# Patent

## Title
Essential and important genes of Pseudomonas aeruginosa and the use thereof to design or identify antibacterial agents

## Abstract

The invention includes a database of candidate essential genes in Pseudomonas aeruginosa, as well as other important genes that, when mutated, lead to a growth attenuated phenotype. Such genes and mutants of such genes are important for identifying antibacterial agents suitable for treating and preventing Pseudomonas aeruginosa infections. The invention includes methods for confirming the essentiality or importance of candidate genes, as well as methods for utilizing those genes to screen for new antibacterial drugs. The invention also includes the antibacterial agents identified using the disclosed methods, as well as methods of using the same for treating and preventing Pseudomonas infection.

## Background
CROSS REFERENCE RELATED TO RELATED APPLICATIONS
This application is a continuation-in-part of co-pending application Ser. No. 11/176,497 filed Jul. 8, 2005, which is a continuation of co-pending application Ser. No. 11/014,899 filed Dec. 20, 2004, which is a continuation of application Ser. No. 10/480,838, filed Dec. 15, 2003 which is a National Stage application of PCT/US02/19153 filed Jun. 17, 2002, which was published in English under PCT Article 21(2) on Dec. 27, 2002. PCT/US02/19153 claims the benefit of U.S. Provisional Ser. No. 60/298,109, filed on Jun. 15, 2001 and U.S. Provisional Ser. No. 60/372,095, filed on Apr. 15, 2002. This application also is a continuation-in-part of co-pending application Ser. No. 10/511,151 filed Oct. 14, 2004, which is a National Stage application of PCT/US02/35518 filed Nov. 5, 2002. PCT/US02/35518 claims the benefit of U.S. Provisional application Ser. No. 60/327,095 filed Apr. 15, 2002. Each of these applications is incorporated in its entirety by reference herein.


FIELD OF INVENTION
The present invention relates to the identification of essential and important genes in Pseudomonas aeruginosa, and the use thereof in screening assays and diagnostic methods to identify, evaluate or design antibacterial agents useful for the treatment of Pseudomonas infections. Such agents are particularly useful in preventing and treating opportunistic infections in immunocompromised individuals and for treating and preventing pulmonary infections in patients having cystic fibrosis disease. Also disclosed is a Bayessian statistical model that may be utilized to increase the statistical confidence that any given gene identified using the disclosed methodology is essential.
BACKGROUND OF INVENTION
Pseudomonas aeruginosa is a versatile Gram-negative bacterium that is able to adapt to and thrive in many ecological niches, from water and soil to plant and animal tissues. The bacterium is capable of utilizing a wide range of organic compounds as food sources, thus giving it an exceptional ability to colonize ecological niches where nutrients are limited, such as soil, marshes and coastal marine habitats. Hardalo, C. & Edberg, S. C. Pseudomonas aeruginosa: assessment of risk from drinking water. Crit. Rev. Microbiol. 23,47-75 (1997). It also forms biofilms on wet surfaces such as those of rocks and soil. Costerton, J. W., Stewart, P. S. & Greenberg, E. P. Bacterial biofilms: a common cause of persistent infections. Science 284,13181322 (1999).Aheam, D. G., Borazjani, R. N., Simmons, R. B. & Gabriel, M. M. Primary adhesion of Pseudomonas aeruginosa to inanimate surfaces including biomaterials. Methods Enzymol. 310, 551-557 (1999). Analysis of the P. aeruginosa genome has identified genes involved in locomotion, attachment, transport and utilization of nutrients, antibiotic efflux, and two component and other regulatory systems involved in sensing and responding to environmental changes. Because its natural habitat is the soil, where it exposed to bacilli, actinomycetes and molds, it has developed resistance to a variety of their naturally-occurring antibiotics.
The emergence of P. aeruginosa as a major opportunistic human pathogen during the past century may be a consequence of its resistance to the antibiotics and disinfectants that eliminate other environmental bacteria. P. aeruginosa is now a significant source of bacteraemia in burn victims, urinary-tract infections in catheterized patients, and hospital-acquired pneumonia in patients on respirators. Bodey, G. P., Bolivar, R., Fainstein, V. & Jadeja, L. Infections caused by Pseudomonas aeruginosa. Rev. Infect. Dis. 5, 279-313 (1983). It is also the predominant cause of morbidity and mortality in cystic fibrosis patients, whose abnormal airway epithelia allow long-term colonization of the lungs by P. aeruginosa. Thus, people with cystic fibrosis, burn victims, individuals with cancer and AIDS, and patients requiring extensive stays in intensive care units are particularly at risk of disease resulting from P. aeruginosa infection. P. aeruginosa is also a cause of a variety of different disorders including septicemia, urinary tract infections, pneumonia and chronic lung infections, endocarditis, dermatitis, osteochondritis, ear and eye infections, bone and joint infections, gastrointestinal infections and skin and soft tissue infections, including wound infections, pyoderma and dermatitis.
Cystic fibrosis is one of the most common fatal genetic disorders in the United States, affecting about 30,000 individuals. A comparable number of people in Europe also have CF. It is most prevalent in the Caucasian population, occurring in one of every 3,300 live births. The gene involved in cystic fibrosis was identified in 1989 and codes for a protein called the cystic fibrosis transmembrane conductance regulator (CFTR). This protein, normally produced in a number of tissues throughout the body, regulates the movement of salt and water in and out of these cells. One hallmark of CF is the presence of a thick mucus secretion that clogs the bronchial tubes in the lungs and plugs the exit passages from pancreas and intestines, leading to loss of function of these organs and resulting in a predisposition toward chronic bacterial infections. Pseudomonas aeruginosa, having a propensity to live in warm, wet environments, is a particular problem for CF patients, whose lungs typically become colonized (inhabited long-term) by P. aeruginosa before their 10th birthday. Although antibiotics can decrease the frequency and duration of these attacks, resistant bacteria are quick to develop and the bacteria are never completely eradicated from the lung. More effective antibiotics are necessary for improving lung function and quality of life for CF patients for extended time periods.
Pseudomonas aeruginosa is notorious for its resistance to antibiotics and is, therefore, a particularly dangerous and dreaded pathogen. Todor, K. 2000 Pseudomonas aeruginosa, University of Wisconsin-Madison, available on Apr. 25, 2001 at the URL address: http file type, www host server, domain name bact.wisc.edu, microtextbook/disease directory. The permeability barrier afforded by its outer membrane LPS also contributes to its natural antibiotic resistance, as do the presence of two antibiotic resistance plasmids, both R-factors and RTFs, which are commonly transferred between cells by the bacterial processes of transduction and conjugation. Only a few antibiotics are effective against Pseudomonas, including tobramyocin (TOBI; Chiron), fluoroquinolone, gentamicin and imipenem, and even these antibiotics are not effective against all strains.
Pseudomonas aeruginosa disease generally begins with some alteration or circumvention of normal host defenses and may involve several different virulence determinants. Todor, 2000, supra. The ultimate Pseudomonas infection may be seen as composed of three distinct stages: (1) bacterial attachment and colonization; (2) local invasion; (3) disseminated systemic disease. Particular bacterial determinants of virulence mediate each of these stages and are ultimately responsible for the characteristic syndromes that accompany the disease. For instance, Pseudomonas utilize fimbriae or pili to adhere to the epithelial cells, apparently via binding to specific galactose or mannose or sialic acid receptors on epithelial cells. Fimbrial adherence may be an important step in Pseudomonas keratitis and urinary tract infections, as well as infections of the respiratory tract. Mucoid strains, which produce an a exopolysaccharide (alginate) have an additional or alternative adhesin which attaches to the tracheobronchial mucin (N-acetylglucosamine). Therefore, mucoid strains of P. aeruginosa are commonly seen in lung infections.
The ability of P. aeruginosa to invade tissues depends upon its resistance to phagocytosis and the host immune defenses, and the extracellular enzymes-and toxins that break down physical barriers and otherwise contribute to bacterial invasion. Todor, 2000, supra. For instance, Pseudomonas elastase cleaves collagen, IgG, IgA, and complement, and also lyses fibronectin to expose receptors for bacterial attachment on the mucosa of the lung. Alkaline protease interferes with fibrin formation and lyses fibrin. Together, elastase and alkaline protease destroy the ground substance of the cornea and other supporting structures composed of fibrin and elastin. Elastase and alkaline protease together are also reported to cause the inactivation of ganmna Interferon (IFN) and Tumior Necrosis Factor (TNF).
P. aeruginosa produces three other soluble proteins involved in invasion, including a cytotoxin (MW 25,000) and two hemolysins. Todor, 2000, supra. The cytotoxin is a pore-forming protein originally named leukocidin because of its effect on neutrophils, but it appears to be cytotoxic for most eukaryotic cells. Of the two hemolysins, one is a phospholipase and the other is a lecithinase. They appear to act synergistically to break down lipids and lecithin. The cytotoxin and hemolysins contribute to invasion through their cytotoxic effects on eukaryotic cells.
Pseudornonas aeruginosa also produces two extracellular protein toxins, Exoenzyme S and Exotoxin A. Exoenzyme S may act to impair the function of phagocytic cells in the bloodstream and internal organs to prepare for invasion by P. aeruginosa, and is typically produced by bacteria growing in burned tissue. Exotoxin A is partially identical to diphtheria toxin, and exhibits a necrotizing activity at the site of bacterial colonization and is thereby thought to contribute to the colonization process. Indirect evidence involving the role of exotoxin A in disease is seen in the increased chance of survival in patients with Pseudomonas septicemia that is correlated with the titer of anti-exotoxin A antibodies in the serum.
While therapeutic measures aimed at any of the above virulence factors may help to slow the progression of an infection and may be useful in combined therapeutic regimens, given the variety of virulence factors of P. aeruginosa, antibacterial agents that inhibit growing bacteria by interacting with essential genes and essential gene products are necessary. Although, this is not to say that genes encoding virulence factors would not be essential to survival in particular niches or environments, emphasizing the importance of screening for gene essentiality in various pathogenic environments. See, e.g., Coulter et al., 1998, Staphylococcus aureus genetic loci impacting growth and survival in multiple infection environments, Mol. Microbiol. 30(2): 393-404. However, as P. aeruginosa becomes more and more resistant to existing antibacterial agents, new compounds are required.
Indeed, reports of bacterial strains resistant to the most powerful known antibiotics are becoming more common, signaling that new antibiotics are needed for all bacteria, not only P. aeruginosa. For instance, the United States Center for Disease Control recently announced that one of the most powerful known antibiotics, vancomycin, was unable to treat an infection of Staphylococcus aureus (staph), an organism commonly found in the environment and responsible for many nosocomial infections. If this trend continues, some have warned that we could return to a time when a common bacterial infection is a life threatening matter. See Zyskind et al., WO 00/44906, published Aug. 3, 2000.
Historically, however, the identification of new antibacterial drugs has been painstaking and laborious with no guarantee of success. Traditional methods involve blindly and randomly testing potential drug candidate molecules, with the hopes that one might be effective. Today, the average cost to discover and develop a new drug is nearly $500 million, and the average time is 15 years from laboratory to patient. New identification and screening methods that shorten and improve this process are much needed.
A newly emerging technique for identifying new antibacterial agents is to first identify gene sequences and proteins required for the proliferation of bacteria, or “essential” genes and proteins, and then conduct a biochemical and structural analysis of that target gene or protein in order to derive compounds that interact with the target. Such methodology employs molecular modeling techniques, combinatorial chemistry and other means to design candidate drugs, and offers a more directed alternative to merely screening random compounds with the hope that one might be suitable for a particular bacterium.
Nevertheless, even this preferred approach presents obstacles including the identification of essential genes and proteins, and the design of new assays for the genes thus identified in order to efficiently screen candidate compounds. Several groups have proposed systems for the identification of essential genes. For instance, Zyskind and colleagues propose a method of identifying essential genes in Escherichia coli by subcloning a library of E. coli nucleic acid sequences into an inducible expression vector, introducing the vectors into a population of E. coli cells, isolating those vectors that, upon activation and expression, negatively impact the growth of the E. coil cell, and characterizing the nucleic acid sequences and open reading frames contained on the subclones identified. See WO 00/44906, herein incorporated by reference. The disadvantage of this method is that the overexpression of nonessential genes can also negatively impact the cell, particularly the overexpression of membrane proteins and sugar transport proteins that are not necessary for growth where alternative carbon sources exist. Such proteins typically become trapped in membrane export systems when the cell is overloaded, and would be identified by this methodology. See Muller, FEMS Microbiol. Lett. 1999 Jul. 1;176(1):219-27.
Another group proposes the identification of growth conditional mutants, and more specifically temperature sensitive (ts) mutants, as a means to identify essential genes in Staphylococcus aureus. See Benton et al., U.S. Pat. No. 6,037,123, issued Mar. 14, 2000, herein incorporated by reference. Each gene is identified by isolating recombinant bacteria derived from growth conditional mutant strains, i.e., following introduction of a vector containing a library of nucleic acid sequences, which would grow under non-permissive conditions but which were not revertants. These recombinant bacteria were found to contain DNA inserts that encoded wild type gene products that replaced the function of the mutated gene under non-permissive growth conditions. By this method, Benton and colleagues were able to identify 38 loci on the S. aureus chromosome, each consisting of at least one essential gene.
The disadvantages of this method are first, the chemical employed to induce mutagenesis (diethyl sulfate, DES) is capable of causing several mutations in the same cell, thereby complicating interpretation of the results. Second, the method is particularly labor intensive in that one must painstakingly analyze replica plates of individual colonies grown at permissive and non-permissive temperatures, where replica plates include both mutant and non-mutant cells. Thus, employing the appropriate level of mutagen to achieve a balance between minimizing the number of non-mutant colonies one must screen in order to identify one mutant, while at the same time avoiding multiple mutations in the same cell, may be an arduous task.
Another group has proposed a transposon mutagenesis system for identifying essential genes called “GAMBIT” (“genomic analysis and mapping by in vitro transposition”), and has used the system to identify essential genes first in the gram positive bacteria Haemophilus influenzae and Streptococcus pneumoniae, and more recently in Pseudomonas aeruginosa. See Akerley et al., Systematic identification of essential genes by In vitro mariner mutagenesis, Proc. Natl. Acad. Sci USA 95(15): 8927-32; Wong and Mekalanos, 2000, Proc. Natl. Acad. Sci. USA 97(18): 10191-96; and Mekalanos et al., U.S. Pat. No. 6,207,384, issued Mar. 27, 2001, herein incorporated by reference. GAMBIT involves first isolating and purifying specific genomic segments of approximately 10 kilobases using extended-length PCR, and creating a high density transposon insertion map of the isolated region using Himar1 transposon mutagenesis. The transposon insertions are then transferred to the chromosome following transformation of the bacteria with the transposon containing vectors, and selection for the antibiotic resistance marker on the transposon. The position of each transposon insertion with respect to a given PCR primer is then determined by genetic footprinting, i.e., by amplifying sub-PCR products using one of the original PCR primers and a primer that recognizes an internal site in the Himer1 transposon. By analyzing the length of PCR fragments thus identified, it is possible to identify regions that are devoid of transposon insertions, thereby signaling regions that might contain essential genes.
While the GAMBIT method is a good technique for looking at a small region of the genome for essential genes, it would be extremely labor intensive to use this method for analyzing the entire genome. This is particularly true for P. aeruginosa, whose genome ( ̃6 megabases) is about 70% greater in size than the H. influenzae genome ( ̃1.8 megabases). Furthermore, GAMBIT would not be readily applicable to use in organisms that are less recombinogenic than H. influenzae. Indeed, while the H. influenzae genome contains about 1700 protein coding genes, P. aeruginosa contains about 5570. According to U.S. Pat. No. 6,207,384, one would need to clone and mutagenize the 6 million base pair genome of P. aeruginosa in 10,000 base pair fragments, isolating and characterizing 400-800 mutants per 10,000 base pair fragment. Generating 6×105 mutants and characterizing them via PCR on gels would require a significant investment of labor, materials and time.
Another group at Abbott Laboratories has proposed a genome scanning method for identification of putative essential genes in H. influeinzae, whereby random transposon insertions are mapped and analyzed to identify open reading frames containing no insertion in order to identify putative essential genes. Reich et al., 1999, Genome Scanning in Haemophilus influenzae for Identification of Essential Genes, J. Bacteriol. 181(16): 4961-68. However, even though transposon insertions were isolated that spanned the whole genome, the authors employed a genomic footprinting technique similar to that used in GAMBIT to map insertions in a short contiguous region of the chromosome. The method further employs the methods of mutation exclusion and zero time analysis in order to monitor the fate of individual insertions after transformation in growing culture, which looks at individual insertions on a case-by-case basis. Again, such techniques would be extremely labor-intensive for the P. aeruginosa genome, which is 70% larger than the genome of H. influenzae. 
Wong and Mekalanos also proposed identifying essential genes in P. aeruginosa by starting with the knowledge of three essential genes in H. influenzae and using genetic footprint analysis to determine if the homologues of these genes are essential in P. aeruginosa. Of three homologues tested, only one was unable to accommodate a transposon insertion. See Wong and Mekalanos, supra. Such results underscore the fact that a gene that is shown to be essential in one species will not necessarily be essential in another, given that some gene products may fulfill different functional roles in different species. Furthermore, given the larger coding capacity of the P. aeruginosa genome relative to that of other bacteria, it would not be surprising for P. aeruginosa to possess an increase in redundant gene functions, thereby decreasing the actual number of essential genes, and making them more difficult to identify.
Another method is entitled Transposon Mediated Differential Hybridisation (TMDH), which is disclosed in WO 01/07651, herein incorporated by reference. This method entails (i) providing a library of transposon mutants of the target organism; (ii) isolating polynucleotide sequences from the library which flank inserted transposons; (iii) hybridising said polynucleotide sequences with a polynucleotide library from said organism; and (iv) identifying a polynucleotide in the polynucleotide library to which said polynucleotide sequences do not hybridise in order to identify an essential gene of the organism. However, the problem with this methodology is that it has a high propensity to lead to false positives, and many essential genes will be missed. Furthermore, the method does not yield any detailed information regarding the loci disrupted by transposons, or whether they were hit more than once.
Thus, there is a great need for more efficient methods to identify essential genes, particularly in P. aeruginosa, so that new antibacterial agents may be designed therefrom for use in treatment of P. aeruginosa infections.
SUMMARY OF INVENTION
The present inventors have devised a database of potential essential or otherwise important genes in P. aeruginosa, which may be used to verify essentiality and design antibacterial agents active against the targets thus identified In particular, the inventors have isolated and mapped a library of at least about 5,000 to at least about 14,000 transposon insertions in the genome of P. aeruginosa, and more preferably a library of at least about 8000 to at least about 14,000 transposon insertions, and even more preferably a library of at least about 10,000 to at least about 14,000 transposon insertions, using the recently published P. aeruginosa gene sequence. The map thus generated was used to form a database of approximately 1500 to 3000 open reading frames, or more preferably about 1500 to 2000 open reading frames, for which no transposon insertions could be obtained, each of which possibly represents an essential gene required for growth and proliferation of P. aeruginosa on rich media, or an important gene, the mutation of which results in an attenuated growth mutant. Also disclosed is a Bayessian statistical model that may be utilized to increase the statistical confidence that any given gene identified using the disclosed methodology is essential.
Thus, one aspect of the invention is a database of putative essential or otherwise important genes, defined by the absence of transposon insertions in those genes in a High Throughput Transposon Insertion Map (HTTIM) database comprising about 10,000 to about 14,000 transposon insertions in the genome of Pseudomnonas aeruginosa. Minimally, such a database comprises approximately 1800 open reading frames (ORFs), each of which may be further tested for essentiality using a variety of tests disclosed herein. However, predictions of essentiality or importance may be bolstered based on length of the ORF and predicted function and other statistical factors, thereby providing for more narrow databases of putative essential genes. Thus, the invention also includes databases that are more narrow and comprise only those genes for which essentiality or importance may be predicted with at least an 80% confidence level, and include at least about 850 to about 875 genes. The invention also includes databases assigned a confidence level of about 85% and including at least about 675 to about 700 genes. The invention further includes databases assigned a confidence level of about 90% including at least about 475 to about 500 genes. Further, the invention includes databases assigned a confidence level of about 95% and including at least about 200 to 250 genes.
The transposon insertion map and database of putative essential or otherwise important open reading frames (ORFs) obtained may be used to confirm the essentiality or importance of genes, for example by integration knock outs in the presence of chromosomal complementation or by integration and activation of a regulatable promoter. An “essential” gene is one that cannot be “knocked out,” i.e. for which null mutants having complete absence of the gene product are not viable. This does not mean, however, that such genes could not tolerate point mutations or truncations that preserve sufficient gene product function so as to enable cell growth and survival. Essential genes are to be distinguished from “important” genes, which are also included in the present invention, in that a “knock out” of an important gene does not lead to cell death but rather results in an attenuated growth mutant. Such genes may be included in the database of open reading frames not hit by random transposon mutagenesis as described herein, because attenuated growth colonies may be significantly smaller than the average P. aeruginosa colony and may have been overlooked when transposon insertion mutants were picked to generate the high throughput transposon insertion database (HTTIM).
Nevertheless, important gene products may interact with or regulate other genes, gene products or cellular processes that are essential, thereby making such gene products appropriate targets for drug design. Moreover, most drugs don't effectively kill all the pathogenic bacteria in the body, rather, they kill or growth attenuate a portion of the bacteria, empowering the immune system to target the remainder. Hence, important genes that, when targeted with an antibacterial agent, result in attenuated growth, are also targets for the antibacterial drugs of the present invention.
The invention also includes a database of attenuated growth mutants identified from the HTTIM transposon database. The genes marked by such mutations are of the same class of importance as the “important” genes identified in the no-hit database of genes, except that the growth attenuated nature of such transposon mutants was discovered at the transposon mutagenesis stage, rather than at the stage where essentiality is tested via targeted knock out. Thus, genes that when mutated confer attenuated growth may be identified from two sources: (1) from the library of open reading frames that did not receive a transposon insertion during HTTIM but were subsequently identified as an important gene when essentiality was tested via knock out and/or promoter swap strategies, and (2) from the HTTIM database itself when in the process of accumulating transposon insertion mutants it was observed that a particular insertion conferred an attenuated growth phenotype.
Such attenuated mutants grow more slowly than wild type, and may grow more slowly due to reduced expression of an essential gene, i.e., transposon is in gene that regulates expression of an essential gene, or due to expression of a truncated form of an essential gene, i.e., transposon is in the essential gene itself and leads to expression of a truncated mRNA. For example, mutants that show a higher drug susceptibility could be the result of insertions in a gene that potentiates resistance, such an efflux pump, or due to reduced expression of essential genes involved in the mechanism of action of the drug. Expression of mutated forms of essential and important genes may make the cell more susceptible to compounds that inhibit that particular gene or gene product, and may allow the identification of antibacterial agents with greater sensitivity. Furthermore, screening in whole cells overcomes the potential problems of uptake and efflux that are sometimes an issue for compounds identified via enzyme-based assays.
The essential and important genes of the invention may be used to design, screen for and evaluate potential antibacterial agents for the purpose of developing new treatments for P. aeruginosa infection. Antibacterial agents identified according to the invention may have activity against the gene or against the corresponding gene product or metabolic pathways requiring the gene product. For instance, antibacterial agents according to the invention may include antisense nucleic acids or regulatory proteins that bind to open reading frames, to upstream polar sequences or to promoters that drive expression of the genes encoded by such open reading frames. Active agents according to the invention may also include antibodies or proteins that bind to proteins encoded by open reading frames, or to transcriptional or translational regulators of such genes or proteins, or to binding partners of such proteins. Agents may also be chemical compounds designed following molecular modeling of essential gene products according to the invention, or mutant proteins designed therefrom that compete with the essential wild type protein for reactive cell components or for interacting nutrients, as well as agents from random chemical.
The present invention therefore includes methods and assays for identifying antibacterial agents having specificity for the essential or important open reading frames identified, or to genes and proteins that interact with such open reading frames or the products encoded thereby. Once essential and important open reading frames are identified, antibacterial agents may be identified using the assays and methods described herein, or by any suitable assay. Such assays may vary depending on the function delineated for each essential locus, as would be apparent to those of skill in the art. For instance, enzyme assays may be designed based on the predicted function of essential and important genes in order to define classes of inhibitors to be tested. Also, random chemical libraries may be screened for activity against the isolated genes or gene products. Cell lines may be designed or isolated that demonstrate reduced expression of essential genes, thereby providing a sensitive screening tool for inhibitors that effect the activity of that gene or gene product as it functions in the cell. Such cell lines may be devised from cells having transposon insertions that lead to attenuated growth, or may be constructed by the promoter swap techniques described herein, by using a regulatable promoter that can be used to increase gene expression, allowing for confirmation of target specificity. Here, the minimal inhibitory concentration of the inhibitor is directly related to the expression level of the target gene, such that under low expression, an attenuated growth cell is more susceptible to an inhibitor than the wild type strain, and as you raise the expression level, the minimum inhibitory concentration (MIC) increases. The MIC shift will be consistent when the inhibitor acts on the regulated target.
Active agents and compounds can be formulated into pharmaceutical compounds and compositions, effective for treating and preventing Pseudomonas infections in accordance with the methods of the invention. Such therapy will be particularly useful in the hospital setting for preventing and treating nosocomial infections, and for administering to cystic fibrosis patients to improve lung function and quality of life. Depending on the activity of the essential or important gene targeted, such agents could also be useful in treating all types of Pseudomonas infections ranging from bacteraemia and septicemia, urinary-tract infections, pneumonia and chronic lung infections, burn infections, cancer, AIDS, endocarditis, dermatitis, osteochondritis, ear and eye infections, bone and joint infections, gastrointestinal infections and skin and soft tissue infections, including wound infections, pyoderma and dermatitis. Further, the invention provides pharmaceutical compositions appropriate for use in methods of treating bacterial infections described above.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1. Depiction of a single crossover recombination event resulting in integration of a plasmid into the bacterial chromosome. Isolation of such recombinants indicates that the targeted gene is not essential.
FIG. 2. Single crossover and integration of a plasmid resulting in the replacement of a wild type promoter with a regulatable promoter.
FIG. 3. Depiction of the ‘promoter swap’ strategy, using transformation of pBEM10 into P. aeruginosa in order to replace the lpxC promoter with the arabinose araBAD promoter, thereby allowing modulation of its lpxC expression by the use of a simple sugar, arabinose.
FIG. 4. Graph showing the susceptibility or non-susceptibility of various E. coli and P. aeruginosa strains to the inhibitor L161,240.
FIG. 5. Graph depicting the effect of tetracycline and L161,240 on the growth of P. aeruginosa strain PA01 with and without polymixin permeabilization.
FIG. 6. Sensitivity of various E. coli and P. aeruginosa strains to inhibitor L161,240 following promoter swap and transformation with vector expressing E. coli lpxC or P. aeruginosa lpxC. E. coli “swaps” refer to P. aeruginosa containing a vector comprising E. coli lpxC, and “PA swaps” refer to P. aeruginosa containing a vector comprising P. aeruginosa lpxC.
FIG. 7. Graph illustrating ORF coverage by Tn5 achieved in High-Throughput Transposon Insertion Mapping (HTTIM, wherein 30% of the genes in the genome are candidate essential genes where ORF size is not taken into account in predicting essentiality.
FIG. 8. Graph depicting the probability of identifying an essential gene given no transposon insertion, as a function of gene size.
FIG. 9. A circular map of the P. aeruginosa genome showing distribution of transposon insertion sites constituting a HTTIM of the invention, and demonstrating the random nature of the transposon employed. The length of the bars radiating outward from the center of the circular map reflect the number of transposon insertions per non-overlapping kilobase.
FIG. 10. Histogram depicting the number of ORFs in the P. aeruginosa genome. FIG. 10A, up to 4000 base pairs. FIG. 10B, from 4000 up to 16884 base pairs.
FIG. 11. Graph showing likelihood and accumulative likelihood gains.
FIG. 12. Trajectory of the algorithm projected in a subspace spanned by two gene sizes. The x-axis represents genes of sizes 151-160 DNA base-pairs and y-axis represents genes of sizes 171-180 DNA basepairs. Here n=(2,1) and M=(7,9). The median gene size of each group is used as the gene size. At iteration number 66, the likelihood gain is maximum in the direction of increasing the number of nonessential genes by one for genes with size 171-180 DNA base-pairs. At iteration number 443, the largest likelihood gain is obtained in the direction of increasing one nonessential genes for genes of sizes 151-160 DNA base pair. At any point, moving backwards has a negative likelihood gain.
FIG. 13. More trajectories of the searching algorithm projected in different subspaces.
FIG. 14. Plot of likelihood for different initial values.
FIG. 15. Trajectories of the algorithm with different starting values projected in the subspace spanned by two gene sizes: 1101-1150 DNA base-pairs for X-axis and 921-930 DNA basepairs for y-axis.
FIG. 16. FIG. 16A The top line is M, number of genes, the bottom line is n, the number of genes with at least one observed insertion; the line in the middle is N, the number of estimated nonessential genes. For demonstration purpose, a cubic spline smooth is applied to the data. FIG. 16B, histogram of resamples of γ (left) and λ (right).
FIG. 17. Plot of {circumflex over (N)}1/M1. The doted line is the value of {circumflex over (N)}1/M1 and the solid line is a moving average smooth.



The essential and important open reading frames identified in the present invention were originally part of a library of putative nucleic acid sequences generated from P. aeruginosa strains PA01 and PAK. See Table 1. Nevertheless, it is expected that the genes identified will also be essential or important in related P. aeruginosa strains as well as other Pseudomonas species, given the low sequence diversity that exists between P. aeruginosa strains of widely diverse environments and the pronounced structural and functional homology of gene products. See, e.g., Spangenberg et al., 1998, Structural and functional implications of sequence diversity of Pseudomonas aeruginosa genes oriT, ampC and fliC, Electrophoresis 19(4): 545-50; Ruimy et al., 2001, Genetic diversity of Pseudomnonas aeruginosa strains isolated from ventilated patients with nosocomial pneumonia, cancer patients, bacteremia, and environmental water, Infect. Immun. 69(1): 584-8. For instance, comparative sequencing of several P. aeruginosa genes from several environmental and clinical isolates revealed the sequence diversity to be about one order of magnitude lower than in comparable housekeeping genes from Salmonella. See Kiewitz and Tummler, 2000, Sequence diversity of Pseudomonas aeruginosa: impact on population structure and genome evolution, J. Bacteriol. 182(11): 3125-35. Thus, it is expected that agents identified as antibacterial based on their interaction with genes or gene products of P. aeruginosa PA01 or PAK will be broadly applicable as antibacterial agents against a variety of Pseudomonas species as well as other bacteria including but not limited to Escherichia, Hemophilts, Vibrio, Borrelia, Enterococcus, Heliobacter, Legionella, Mycobacterium, Mycoplasma, Neisseria, Staphylococcus, Streptococcus, etc.
Thus, the present invention encompasses an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide having at least 80% sequence identity to a polypeptide encoded by a nucleic acid sequence selected from the group consisting of the Pseudomonas aeruginosa open reading frames (ORFs) listed in Table 1. More preferably, the present invention encompasses an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide having at least about 85 to 90% sequence identity to a polypeptide encoded by a nucleic acid sequence selected from the group consisting of the Pseudomonas aeruginosa open reading frames (ORFs) listed in Table 1. Even more preferably, the present invention encompasses an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide having at least about 90 to about 95% sequence identity to a polypeptide encoded by a nucleic acid sequence selected from the group consisting of the Pseudomonas aeruginosa open reading frames (ORFs) listed in Table 1.
In particular, the invention encompasses isolated nucleic acid molecules comprising nucleic acid sequences encoding polypeptides having at least 80% sequence identity, or more preferably at least about 85 to 90 to 95% identity, to a polypeptide encoded by an essential or important nucleic acid sequence selected from the group consisting of the Pseudomonas aeruginosa open reading frames (ORFs) listed in Table 1, wherein essentiality or importance of said nucleic acid sequence is determined by integration knock-out coupled with extra-chromosomal complementation. Likewise, the invention encompasses isolated nucleic acid molecules comprising nucleic acid sequences encoding polypeptides having at least 80% sequence identity, or more preferably at least about 85 to 90 to 95% identity, to a polypeptide encoded by an essential nucleic acid sequence selected from the group consisting of the Pseudonmonas aeruginosa open reading frames (ORFs) listed in Table 1, wherein essentiality or importance of said nucleic acid sequence is determined by integration of a regulatable promoter into the gene, or via any other suitable method.
In one embodiment, the polynucleotides of the invention are recombinant. Recombinant polynucleotides of the invention include proteins of genomic, cDNA, semisynthetic, or synthetic origin, which, by virtue of its origin or manipulation (1) is not associated with all or a portion of a polynucleotide with which it is associated in nature; (2) is linked to a polynucleotide other than that to which it is lined in nature; or (3) does not occur in nature.
Given that the library of nucleic acid sequences encompassed in Table 1 provides an unprecedented tool useful for the identification of essential and otherwise important genes in Pseudomonas and the construction and isolation of attentuated mutants, the present invention includes a library of nucleic acid sequences consisting essentially of nucleic acid sequences having at least 70% sequence identity, or more preferably at least about 80 to 90 to 95% identity, to a nucleic acid sequence selected from the group consisting of the Pseudomonas aeruginosa open reading frames (ORFs) listed in Table 1, wherein said library of nucleic acid sequences is employed to identify essential or otherwise important genes or to construct or isolate attenuated mutants in Pseudomonas. 
Also encompassed in the invention is a map of at least about 10,000 to about 14,000 transposon insertions in the genome of Pseudomonas aeruginosa (High-Throughput Transposon Insertion Database or HTTIM), wherein said map is useful for identifying genes that are essential or important for survival of said Pseudomonas aeruginosa, i.e., by permitting the generation of a database of open reading frames that do not contain a transposon insertion. FIG. 9 contains a circular map of the P. aeruginosa genome depicting 12,000 to 13,000 transposon insertion sites constituting a HTTIM of the invention, and demonstrates the random nature of the transposon employed. The length of the bars radiating outward from the center of the circular map reflect the number of transposon insertions per non-overlapping kilobase. Table 3 contains a list of 13,515 specific Tn5 transposon insertion sites generated in either PAK or PA01, with the 473 mutants 12516-13043 being identified as attenuated for growth.
Thus, the databases and libraries disclosed herein may be used to formulate useful subsets of these libraries and databases. Accordingly, the invention includes subsets of the databases and libraries disclosed. For instance, mutants 12516-13043 are identified as attenuated for growth and as such, the genes in this subset could be useful drug targets. Accordingly, this group of 473 mutants from the HTTIM database of 13,515 transposon hits provides a useful subset database for comparing homologies with essential genes of other organisms, for computer modeling of potential antibacterial agents, etc. A particularly useful database subset is one containing essential genes from P. aeruginosa that are also identified as essential in other Gram negative or Gram positive bacteria. Indeed, genes that have essential homologs in other bugs are likely to provide useful targets for broad spectrum antibacterial agents, i.e., agents that have broad spectrum activity as an antibacterial agent. Genes in the putative essential or important gene database have already been identified via BLAST or other database analyses, and constitute an exemplary subset database of the present invention. See Table 4.
Further, the databases and subset databases of the present invention may also be used as comparative tools with other like databases or database subsets to identify broad spectrum. For instance, particularly envisioned is an embodiment wherein the database of putative essential and important genes identified in P. aeruginosa is cross-referenced with a similar database formed from S. aureus, wherein homologues present in both databases signal a potential target for a broad spectrum antibacterial agent. Cross-referencing between P. aeruginosa and S. aureus in particular will identify antibacterial targets for identifying broad spectrum antibiotics active against both Gram negative and Gram positive bacteria. However, databases derived from any bacteria could be employed in such comparisons, as well as databases formed from yeast, fungi, mycoplasma, and other potential pathogens.
Also encompassed in the invention is the use of essential and important genes and the corresponding proteins expressed thereto in the design of vaccines for eliciting prophylactic or therapeutic immune responses against Pseudomnonas aeruginosa. 
Such vaccines will typically comprise a Pseudomonas aeruginosa protein antigen or fragment or variant thereof encoded by an essential gene. Additionally, such antigens will preferably be a protein expressed on the surface of the bacteria.
Such vaccines will typically comprise a Pseudomonas aeruginosa protein antigen or fragment or derivative thereof encoded by an essential or important gene. Preferably, the protein antigen expressed from a recombinant polynucleotide.
Where the invention is directed to a fragment of a protein encoded by an essential or important gene, said fragment is preferably at least 8 to 12 amino acids long, and even more preferably at least about 20 to 30 amino acids long. Preferably, the fragment comprises either a B cell or a T cell epitope.
Where the invention is directed to a derivative of a protein encoded by an essential or important gene, said derivative contains one or more amino acid substitutions, additions or deletions. Preferably, the amino acid substitutions are conservative amino acid replacements. Conservative amino acid replacements are those that take place within a family of amino acids that are related in their side chains. Genetically encoded amino acids are generally divided into four families: (1) acidic=aspartate, glutamate; (2) basic=lysine, arginine, histidine; (3) non-polar=alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan; and (4) uncharged polar=glycine, asparagine, glutamine, cystine, serine, threonine, tyrosine. Phenylalanine, tryptophan, and tyrosine are sometimes classified jointly as aromatic amino acids. For example, it is reasonably predictable that an isolated replacement of a leucine with an isoleucine or valine, an asparate with glutamate, a threonine with a serine, or a similar conservative replacement of an amino acid with a structurally related amino acid will not have a major effect on the biological activity. Polypeptide molecules having substantially the same amino acid sequence as the protein by possessing minor amino acid substitutions that do not substantially affect the functional aspects are encompassed with the scope of derivatives of the proteins of the invention.
The polypeptide fragment or derivative is preferably immunologically identifiable with the polypeptide encoded by the essential or important gene. The polypeptide fragment or derivative is preferably immunogenic and is able to cause a humoral and/or cellular immune response, either alone or when linked to a carrier, in the presence or absence of an adjuvant. The polypeptide fragment or derivative may be fused to or incorporated into another polypeptide sequence. This other polypeptide sequence may include one or more other proteins, fragments or derivatives thereof encoded by an essential or important gene. The other polypeptide sequence may also include a polypeptide sequence which allows for presentation of the polypeptide fragment or derivative.
Accordingly, the present invention encompasses an isolated polypeptide and fragments and derivatives thereof, wherein said polypeptide has at least 80% sequence identity to a polypeptide encoded by a nucleic acid sequence selected from the group consisting of the Pseudomonas aeruginosa open reading frames (ORFs) listed in Table 1. More preferably, the present invention encompasses an isolated polypeptide and fragments and derivatives thereof, wherein said polypeptide has at least about 85 to 90% sequence identity to a polypeptide encoded by a nucleic acid sequence selected from the group consisting of the Pseudomonas aeruginosa open reading frames (ORFs) listed in Table 1. Even more preferably, the present invention encompasses an isolated polypeptide and fragments and derivatives thereof, wherein said polypeptide has at least about 90% to about 95% sequence identity to a polypeptide encoded by a nucleic acid sequence selected from the group consisting of the Pseudomonas aeruginosa open reading frames (ORFs) listed in Table 1.
In particular, the invention encompasses isolated polypeptides and fragments and derivatives thereof, wherein said polypeptides have at least 80% sequence identity, or more preferably at least about 85 to 90 to 95% identity, to a polypeptide encoded by an essential or important nucleic acid sequence selected from the group consisting of the Pseudomonas aeruginosa open reading frames (ORFs) listed in Table 1, wherein the essentiality or importance of said nucleic acid sequence is determined by integration knock-out couple with extra-chromosomal complementation. Likewise, the invention encompasses isolated polypeptides and fragments and derivatives thereof, wherein said polypeptides have at least 80% sequence identify, or more preferably at least about 85 to 90 to 95% identity, to a polypeptide encoded by an essential nucleic acid sequence selected from the group consisting of the Pseudomonas aeruginosa open reading frames (ORFs) listed in Table 1, wherein essentiality or importance of said nucleic acid sequence is determined by integration of a regulatable promoter into the gene, or via any other suitable method.
Also encompassed in the invention are therapeutic and prophylactic vaccines that comprise ligands that specifically bind antigens encoded by essential or important genes identified according to the invention, for use in, for instance, passive immunization. Preferred ligands are antibodies and antibody fragments that specifically bind the antigen encoded by the essential gene. Such antibodies may be polyclonal or monoclonal. Types of antibodies and antibody fragments include by way of examples murine antibodies, chimeric, antibodies, humanized antibodies, Fab fragments, Fab2 fragments and human antibodies and scFv's. Methods for producing antibodies and antibody fragments by recombinant and non-recombinant methods are well known to those skilled in the art. In some embodiments the antigen used in such passive immunization may be attached to a cytotoxic moiety, e.g., a radionuclide or other agent that is cytotoxic against the bacteria.
Further encompassed within the scope of the invention are cells or viral vectors that express on their surface a Pseudomonas aeruginosa essential gene, fragment or variant identified according to the invention.
In the case of prophylactic vaccines, the vaccine will comprise an immunogenic composition comprising a prophylactically effective amount of an antigen, antibody, cells or vector expressing an antigen encoded by an essential or important gene and will be formulated such that upon administration it elicits a protective immune response. In the case of therapeutic vaccines, the vaccine will comprise an immunogenic composition comprising a therapeutically effective amount of an antigen, antibody, cells or vectors expressing an antigen encoded by an essential or important gene and will be formulated such that upon administration it elicits a therapeutic immune response. Dosage effective amounts of prophylactic and therapeutic vaccines will be determined by known methods and will typically vary from about 0.00001 g/kg body weight to about 5-10 g/kg body weight.
The immunogenic compositions of the invention can be administered by known methods, i.e., mucosally or parenterally.
Suitable routes of mucosal administration include oral, intranasal (IN), intragastric, pulmonary, intestinal, rectal, ocular, and vaginal routes. Preferably, mucosal administration is oral or intranasal.
Where mucosal administration is used, the immunogenic composition is preferably adapted for mucosal administration. For instance, where the composition is administered orally, it may be in the form of tablets or capsules (optionally enteric-coated), liquid, transgenic plants, etc. Where the composition is administered intranasally, it may be in the form of a nasal spray, nasal drops, gel or powder. Where the antigen composition is adapted for mucosal administration, it may further be formulated such that the antigen remains stable, for instance by the use of carriers and excipients.
The immunogenic compositions of the invention can further comprise a mucosal adjuvant. Mucosal adjuvants suitable for use in the invention include (a) E.coli heat-labile enterotoxin (“LT”), or detoxified mutants thereof, such as the K63 or R72 mutants; (B) cholera toxin (“CT”), or detoxified mutants thereof; or (C) microparticles (i.e., a particle of  ̃100 nm to  ̃150 μm in diameter, more preferably  ̃200 nm to  ̃30 μm in diameter, and most preferably  ̃500 nm to  ̃10 μm in diameter) formed from materials that are biodegradable and non-toxic (e.g. a poly(α-hydroxy acid), a polyhydroxybutyric acid, a polyorthoester, a polyanhydride, a polycaprolactone etc.); (D) a polyoxyethylene ether or a polyoxyethylene ester (see International patent application WO 99/52549); (E) a polyoxyethylene sorbitan ester surfactant in combination with an octoxynol (see International patent application WO 01/21207) or a polyoxyethylene alkyl ether or ester surfactant in combination with at least-one additional non-ionic surfactant such as an octoxynol (see International patent application WO 01/21152); (F) chitosan (e.g. International patent application WO 99/27960) and (G) an immunostimulatory oligonucleotide (e.g. a CpG oligonucleotide) and a saponin (see International patent application WO 00/62800). Other mucosal adjuvants are also available (e.g. see chapter 7 of Vaccine design: the subunit and adjuvant aproach, eds. Powell & Newman, Plenum Press 1995 (ISBN 0-306-44867-X).
Mutants of LT are preferred mucosal adjuvants, in particular the “K63” and “R72” mutants (e.g. see International patent application WO 98/18928), as these result in an enhanced immune response.
Microparticles are also preferred mucosal adjuvants. These are preferably derived from a poly(α-hydroxy acid), in particular, from a poly(lactide) (“PLA”), a copolymer of D,L-lactide and glycolide or glycolic acid, such as a poly(D,L-lactide-co-glycolide) (“PLG” or “PLGA”), or a copolymer of D,L-lactide and caprolactone. The microparticles may be derived from any of various polymeric starting materials which have a variety of molecular weights and, in the case of the copolymers such as PLG, a variety of lactide:glycolide ratios, the selection of which will be largely a matter of choice, depending in part on the coadministered antigen.
Antigen may be entrapped within the microparticles, or may be adsorbed to them.
Entrapment within PLG microparticles is preferred. PLG microparticles are discussed in further detail in Morris et al., (1994), Vaccine, 12:5-11, in chapter 13 of Mucosal Vaccines, eds. Kiyono et al., Academic Press 1996 (ISBN 012410587), and in chapters 16 & 18 of Vaccine design: the subunit and adjuvant aproach, eds. Powell & Newman, Plenum Press 1995 (ISBN 0-306-44867-X).
LT mutants may advantageously be used in combination with microparticle-entrapped antigen, resulting in significantly enhanced immune responses.
Suitable routes of parenteral administration include intramuscular (IM), subcutaneous, intravenous, intraperitoneal, intradermal, transcutaneous, and transdermal (see e.g., International patent application WO 98/20734) routes, as well as delivery to the interstitial space of a tissue.
The immunogenic compositions of the invention may be adapted for parenteral administration (e.g., in the form of an injectable, which will typically be sterile and pyrogen-free).
The immunogenic composition may further comprise a parenteral adjuvant. Parenteral adjuvants suitable for use in the invention include: (A) aluminum compounds (e.g. aluminum hydroxide, aluminum phosphate, aluminum hydroxyphosphate, oxyhydroxide, orthophosphate, sulfate etc. (e.g. see chapters 8 & 9 of Vaccine design: the subunit and adjuvant aproach, eds. Powell & Newman, Plenum Press 1995 (ISBN 0-306-44867-X) (hereinafter “Vaccine design”), or mixtures of different aluminum compounds, with the compounds taking any suitable form (e.g. gel, crystalling, amorphous etc.), and with adsorption being preferred; (B) MF59 (5% Squalene, 0.5% Tween 80, and 0.5% Span 85, formulated into submicron particles using a microfluidizer) (see Chapter 10 of Vaccine design; see also International patent application WO 90/14837); (C) liposomes (see Chapters 13 and 14 of Vaccine design); (D) ISCOMs (see Chapter 23 of Vaccine design); (E) SAF, containing 10% Squalane, 0.4% Tween 80, 5% pluronic-block polymer L121, and thr-MDP, either microfluidized into a submicron emulsion or vortexed to generate a larger particle size emulsion (see Chapter 12 of Vaccine design); (F) RibiTM adjuvant system (RAS), (Ribi Immunochem) containing 2% Squalene, 0.2% Tween 80, and one or more bacterial cell wall components from the group consisting of monophosphorylipid A (MPL), trehalose dimycolate (TDM), and cell wall skeleton (CWS), preferably MPL+CWS (DetoxTM); (G) saponin adjuvants, such as QuilA or QS21 (see Chapter 22 of Vaccine design), also known as StimulonTM; (H) ISCOMs, which may be devoid of additional detergent (International patent application WO 00/07621); (I) complete Freund's adjuvant (CFA) and incomplete Freund's adjuvant (IFA); (J) cytokines, such as interleukis (e.g. IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL-12, etc.), interferons (e.g interferon-γ), macrophage colony stimulating factor, tumor necrosis factor, etc. (see Chapters 27 & 28 of Vaccine design); (K) microparticles (see above); (L) monophosphoryl lipid A (MPL) or 3-O-deacylated MPL (3dMPL) (e.g. chapter 21 of Vaccine design); (M) combinations of 3dWPL with, for example, QS21 and/or oil-in-water emulsions (European patent applications 0835318, 0735898 and 0761231); (N) oligonucleotides comprising CpG motifs (see Krieg (2000) Vaccine, 19:618-622; Krieg (2001) Curr. Opin. Mol. Ther., 2001, 3:15-24; WO 96/02555, WO 98/16247, WO 98/18810, WO 98/40100, WO 98/55495, WO 98/37919 and WO 98/52581, etc.) Le. containing at least one CG dinucleotide, with 5-methylcytosine optionally being used in place of cytosine; (O) a polyoxyethylene ether or a polyoxyethylene ester (International patent application WO 99/52549); (P) a polyoxyethylene sorbitan ester surfactant in combination with an octoxynol (International patent application WO 01/21207) or a polyoxyethylene alkyl ether or ester surfactant in combination with at least one additional non-ionic surfactant such as an octoxynol (International patent application WO 01/21152); (Q) an immunostimulatory oligonucleotide (e.g. a CpG oligonucleotide) and a saponin (International patent application WO 00/62800); R) an immunostimulant and a particle of metal salt (International patent application WO 00/23105); (S) a saponin and an oil-in-water emulsion (International patent application WO 99/11241); (T) a saponin (e.g. QS21)+3dMPL+IL-12 (optionally+a sterol) (International patent application WO 98/57659); and (U) other substances that act as immunostimulating agents to enhance the effectiveness of the composition (e.g. see Chapter 7 of Vaccine design).
Aluminium compounds and MF59 are preferred adjuvants for parenteral use.
The immunognic compositions of the invention may be administered in a single dose, or as part of an administration regime. The regime may include priming and boosting doses, which may be administered mucosally, parenterally, or various combinations thereof.
In some instances the vaccines of the invention may comprise several antigens, fragments or variants encoded by essential genes identified according to the invention. Alternatively, the vaccine may further comprise antigens identified by other methods, or specific to other bacteria, e.g., in order to provide multivalent vaccines.
With respect to libraries according to the invention, a library of polynucleotides or a library of transposon insertion sites is a collection of sequence information, which information is provided in either biochemical form (e.g., as a collection of polynucleotide molecules), or in electronic form (e.g., as a collection of polynucleotide sequences stored in a computer-readable form, as in a computer system and/or as part of a computer program). The sequence information of the polynucleotides can be used in a variety of ways, for instance as a resource for gene discovery, i.e., for identifying and verifying essential and important genes in P. aeruginosa, or for identifying essential or important homologues in other genera or species. A polynucleotide sequence in a library can be a polynucleotide that represents an mRNA, polypeptide, or other gene product encoded by the polynucleotide, and accordingly such a polynucleotide library could be used to formulate corresponding RNA or amino acid libraries according to the sequences of the library members.
The nucleotide sequence information of the library can be embodied in any suitable form, e.g., electronic or biochemical forms. For example, a library of sequence information embodied in electronic form comprises an accessible computer data file (or, in biochemical form, a collection of nucleic acid molecules) that contains the representative nucleotide sequences of essential and important genes and/or insertion mutants that are differentially expressed (e.g., attenuated growth mutants). Other combinations and comparisons of cells affected by various diseases or stages of disease will be readily apparent to the ordinarily skilled artisan. Biochemical embodiments of the library include a collection of nucleic acids that have the sequences of the genes or transposon insertion sites in the library, where the nucleic acids can correspond to the entire gene in the library or to a fragment thereof, as described in greater detail below.
The polynucleotide libraries of the subject invention generally comprise sequence information of a plurality of polynucleotide sequences, where at least one of the polynucleotides has a sequence of any of the sequences in Tables 1-3. By plurality is meant at least 2, usually at least 3 and can include up to all of the sequences included in these tables. The length and number of polynucleotides in the library will vary with the nature of the library, e.g., if the library is an oligonucleotide array, a cDNA array, a, computer database of the sequence information, etc.
Where the library is an electronic library, the nucleic acid sequence information can be present in a variety of media. “Media” refers to a manufacture, other than an isolated nucleic acid molecule, that contains the sequence information of the present invention. Such a manufacture provides the genome sequence or a subset thereof in a form that can be examined by means not directly applicable to the sequence as it exists in a nucleic acid. For example, the nucleotide sequence of the present invention, e.g. the nucleic acid sequences of any of the polynucleotides of Tables 1-3, can be recorded on computer readable media, e.g. any medium that can be read and accessed directly by a computer. Such media include, but are not limited to: magnetic storage media, such as a floppy disc, a hard disc storage medium, and a magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media One of skill in the art can readily appreciate how any of the presently known computer readable mediums can be used to create a manufacture comprising a recording of the present sequence information “Recorded” refers to a process for storing information on computer readable medium, using any such methods as known in the art. Any convenient data storage structure can be chosen, based on the means used for stored information. A variety of data processor programs and formats can be used for storage, e.g. word processing text file, database format, etc. In addition to the sequence information, electronic versions of the libraries of the invention can be provided in conjunction or connection with other computer-readable information and/or other types of computer-readable files (e.g., searchable files, executable files, etc, including, but not87 limited to, for example, search program software, etc.).
By providing the nucleotide sequence in computer readable form, the information can be accessed for a variety of purposes. Computer software to access sequence information is publicly available. For example, the gapped BLAST (Altschul et al. Nucleic Acids Res. (1997) 25:3389-3402) and BLAZE (Brutlag et al. Comp. Chem. (1993) 17:203) search algorithms on a Sybase system can be used to identify open reading frames (ORFs) within the genome that contain homology to ORFs from other organisms.
As used herein, “a computer-based system” refers to the hardware means, software means, and data storage means used to analyze the nucleotide sequence information of the present invention. The minimum hardware of the computer-based systems of the present invention comprises a central processing unit (CPU), input means, output means, and data storage means. A skilled artisan can readily appreciate that any one of the currently available computer-based system are suitable for use in the present invention. The data storage means can comprise any manufacture comprising a recording of the present sequence information as described above, or a memory access means that can access such a manufacture.
“Search means” refers to one or more programs implemented on the computer-based system, to compare a target sequence or target structural motif, or expression levels of a polynucleotide in a sample, with the stored sequence information. Search means can be used to identify fragments or regions of the genome that match a particular target sequence or target motif A variety of known algorithms are publicly known and commercially available, e.g. MacPattern (EMBL), BLASTN and BLASTX (NCBI). A “target sequence” can be any polynucleotide or amino acid sequence of six or more contiguous nucleotides or two or more amino acids, preferably from about 10 to 100 amino acids or from about 30 to 300 nucleotides. A variety of comparing means can be used to accomplish comparison of sequence information from a sample (e.g., to analyze target sequences, target motifs, or relative expression levels) with the data storage means. A skilled artisan can readily recognize that any one of the publicly available homology search programs can be used as the search means for the computer based systems of the present invention to accomplish comparison of target sequences and motifs. Computer programs to analyze expression levels in a sample and in controls are also known in the art.
A “target structural motif,” or “target motif,” refers to any rationally selected sequence or combination of sequences in which the sequence(s) are chosen based on a three-dimensional configuration that is formed upon the folding of the target motif, or on consensus sequences of regulatory or active sites. There are a variety of target motifs known in the art. Protein target motifs include, but arc not limited to, enzyme active sites and signal sequences. Nucleic acid target motifs include, but are not limited to, hairpin structures, promoter sequences and other expression elements such as binding sites for transcription factors.
The present invention encompasses the use of the library of essential and important genes to search for polynucleotide and amino acid sequences in common among the essential and important genes. Such identified sequences can be used to design and develop antibacterial agents and vaccines against Pseudomonas aeruginosa. 
A variety of structural formats for the input and output means can be used to input and output the information in the computer-based systems of the present invention. One format for an output means ranks the relative expression levels of different polynucleotides. Such presentation provides a skilled artisan with a ranking of relative expression levels to determine a gene expression profile.
As discussed above, the “library” as used herein also encompasses biochemical libraries of the polynucleotides of Tables 1-3, e.g., collections of nucleic acids representing the provided polynucleotides. The biochemical libraries can take a variety of forms, e.g., a solution of cDNAs, a pattern of probe nucleic acids stably associated with a surface of a solid support (i.e., an array) and the like. Of particular interest are nucleic acid arrays in which one or more of the sequences of Tables 1-3 is represented on the array. By “array” is meant a an article of manufacture that has at least a substrate with at least two distinct nucleic acid targets on one of its surfaces, where the number of distinct nucleic acids can be considerably higher, typically being at least 10 nt, usually at least 20 nt and often at least 25 nt. A variety of different array formats have been developed and are known to those of skill in the art. The arrays of the subject invention find use in a variety of applications, including gene expression analysis, drug screening, mutation analysis and the like, as disclosed in the above-listed exemplary patent documents.
In addition to the above nucleic acid libraries, analogous libraries of polypeptides are also provided, where the polypeptides of the library will represent at least a portion of the polypeptides encoded by a gene corresponding to one or more of the sequences in Tables 1-3.
“Identity” as it is used in the present invention should be distinguished from “homology” or “homologous.” In the context of the coding sequences and genes of this invention, “homologous” refers to genes whose expression results in expression products which have a combination of amino acid sequence similarity (or base sequence similarity for transcript products) and functional equivalence, and are therefore homologous genes. In general such genes also have a high level of DNA sequence similarity (i.e., greater than 80% identity when such sequences are identified among members of the same genus, but lower when these similarities are noted across bacterial genera), but are not identical. Relationships across bacterial genera between homologous genes are more easily identified at the polypeptide (i.e., the gene product) rather than the DNA level. The combination of functional equivalence and sequence similarity means that if one gene is useful, e.g., as a target for an antibacterial agent, or for screening for such agents, then the homologous gene is probably also useful, but may not react in the same manner or to the same degree to the activity of a specific antibacterial agent.
Nevertheless, the identifcation of one such gene serves to identify a homologous gene through the same relationships as indicated above, and can serve as a starting point to determine whether the homologous gene is also essential, whether it responds to the same antibacterial agents, etc. Typically, such homologous genes are found in other bacterial species, especially, but not restricted to, closely related species. Due to the DNA sequence similarity, homologous genes are often identified by hybridizing with probes from the initially identified gene under hybridizing conditions that allow stable binding under appropriately stringent conditions. For instance, nucleic acids having sequence similarity are detected by hybridization under low stringency conditions, for example, at 50° C. and 10×SSC (0.9 M saline/0.09 M sodium citrate) and remain bound when subjected to washing at 55° C. in 1×SSC. Sequence identity can be determined by hybridization under stringent conditions, for example, at 50° C. or higher and 0.1×SSC (9 mM saline/0.9 mM sodium citrate). Hybridization methods and conditions are well known in the art, see, e.g., U.S. Pat. No. 5,707,829. Nucleic acids that are substantially identical to the provided polynucleotide sequences, e.g. allelic variants, genetically altered versions of the gene, etc., bind to the provided polynucleotide sequences under stringent hybridization conditions. By using probes, particularly labeled probes of DNA sequences, one can isolate homologous or related or substantially identical genes. The equivalent function of the product is then verified using appropriate biological and/or biochemical assays.
Using such hybridization technique for the identification of homologous genes, it will be possible to screen other species of bacteria, particularly other genera of gram negative pathogenic bacteria although gram positive bacteria may also be screened, to determine if any essential or important gene identified herein has a homologue in that particular genus of bacteria. If so, such gene could be cloned and isolated for essentiality in the particular genus, and further tested for sensitivity or susceptibility to the antibacterial agents and inhibitors identified herein. Specific genera of bacteria particularly appropriate for hybridization screening for the presence of homologues of essential and important genes include Escherichia, Hemophilus, Vibrio, Borrelia, Enterococcus, Heliobacter, Legionella, Mycobacterium, Mycoplasma, Neisseria, Staphylococcus, Streptococcus, etc.
“Identity,” on the other hand, is gauged from the starting point of complete homology. Thereafter, identity may be described in terms of percentages according to the number of base changes in the DNA sequence taking into account any gaps. For purposes of the present invention, variants of the invention have a sequence identity greater than at least about 65%, preferably at least about 75%, more preferably at least about 85%, and can be greater than at least about 90% or more as determined by the Smith-Waterman homology search algorithm as implemented in MPSRCH program (Oxford Molecular). A preferred method of calculating percent identity is the Smith-Waterman algorithm, using the following. Global DNA sequence identity must be greater than 65% as determined by the Smith-Waterman homology search algorithm as implemented in MPSRCH program (Oxford Molecular) using an affine gap search with the following search parameters: gap open penalty, 12; and gap extension penalty, 1.
Amino acid sequence variants are also included in the invention. Preferably, naturally or non-naturally occurring protein variants have amino acid sequences which are at least 85%, 90%, or 95% identical to the amino acid sequences identified herein, or to a shorter portion of these sequences. More preferably, the molecules are 98% or 99% identical. Percent sequence identity is determined using the Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 2, BLOSUM matrix of 62. The Smith-Waterman homology search algorithm is taught in Smith and Waterman, Adv. Appl. Math. (1981) 2:482-489.
Also included in the invention are fragments of the nucleic acid sequences and amino acid sequences identified herein, as well as RNAs and RNA fragments corresponding to the DNA sequences disclosed. Such nucleic acid fragments are at least about 10 nucleotides, more preferably at least about 20 to 25 nucleotides, and more preferably at least about 50 to 100 nucleotides, and can include any fragment or variant of a fragment. Such nucleic acid fragments may be used as probes for identifying similar or substantially identical or identical nucleic acid sequences in other genera, or as tools in constructing nucleic acid vectors for knock out and promoter swap experiments. Such amino acid fragments are at least about four amino acids in length, more preferably at least about 8 to 12 amino acids in length, and more preferably at least about 20 to 30 amino acids in length, and more antagonists to test binding interactions of the proteins disclosed herein, or alternatively as immunogens to isolate antibodies that recognize and bind to specific epitopes of a target protein.
Once a gene is identified as being essential or important for Pseudomonas growth on rich media or in any specific environment, the invention also encompasses the identification of antibacterial agents that have specific activity against the essential or important genes or their gene products or the biochemical pathways in which they are involved. In this context, the term “biochemical pathway” refers to a connected series of biochemical reactions normally occurring in a cell, or more broadly a cellular event such as cellular division or DNA replication. Typically, the steps in such a biochemical pathway act in a coordinated fashion to produce a specific product or products or to produce some other particular biochemical action. Such a biochemical pathway requires the expression product of a gene if the absence of that expression product either directly or indirectly prevents the completion of one or more steps in that pathway, thereby preventing or significantly reducing the production of one or more normal products or effects of that pathway.
Thus, an agent specifically inhibits such a biochemical pathway requiring the expression product of a particular gene if the presence of the agent stops or substantially reduces the completion of the series of steps in that pathway. Such an agent, may, but does not necessarily, act directly on the expression product of that particular gene. An “expression product” of a gene means that, in a bacterial cell of interest, the gene is transcribed to form RNA molecules. For those genes that are transcribed into mRNAs, the mRNA is translated to form polypeptides. More generally, in this context, “expressed” means that a gene product is formed at the biological level that would normally have the relevant biological activity (i.e., RNA or polypeptide level).
Thus, the invention includes a method of screening for an antibacterial agent, comprising determining whether a test compound is active against an essential or important bacterial gene identified by the methods herein. The invention also includes a method of screening for an antibacterial agent, comprising determining whether a test compound is active against a protein encoded by an essential bacterial gene identified herein, or active to inhibit the biochemical pathway that involves said protein. The term “antibacterial agent” refers to both naturally occurring antibiotics produced by microorganisms to suppress the growth of other microorganisms, and agents synthesized or modified in the laboratory which have either bactericidal or bacteriostatic activity. An “active” agent in this context will inhibit the growth of P. aeruginosa and possibly related species. The term “inhibiting the growth” indicates that the rate of increase in the numbers of a population of a particular bacterium is reduced. Thus, the term includes situations in which the bacterial population increases but at a reduced rate, as well as situations where the growth of the population is stopped, as well as situations where the numbers of the bacteria in the population are reduced or the population even eliminated. If an enzyme activity assay is used to screen for inhibitors, one can make modifications in uptake/efflux, solubility, half life, etc. to compounds in order to correlate enzyme inhibition with growth inhibition.
Assays may include any suitable method and may be expected to vary on the type of essential gene or protein involved. For instance, one embodiment is a method comprising the steps of:

    
    
        a) contacting said protein or a biologically active fragment thereof with a test compound; and
        b) determining whether said test compound binds to said essential gene product or protein or fragment of said protein;
        wherein binding of said test compound to said polypeptide or said fragment is indicative that said test compound is an antibacterial agent. It is quite common in identifying antibacterial agents, to assay for binding of a compound to a particular polypeptide where binding is an indication of a compound which is active to modulate the activity of the polypeptide. Binding may be determined by any means according to the agent tested and techniques known in the art.
    
    


Also, agents that inhibit binding of two proteins or polypeptides may also be identified, for instance using a yeast two-hybrid system. Such a system will entail cloning the genes encoding each protein and expressing each in a reporter cell system such that interaction between the two proteins is monitored by observing the expression of a reporter gene. For instance, cDNAs cloned in a yeast two-hybrid expression system (Chien et al. (1991) Proc. Natl. Acad. Sci. (U.S.A) 88: 9578; Zervos et al. (1993) Cell 72: 233) can be used to identify other cDNAs encoding proteins that interact with the protein encoded by the first, thereby produce expression of the GAL4-dependent reporter gene. Thereafter, cells expressing both proteins leading to expression of the reporter gene are used to screen for agents that interact with either protein, or the gene encoding either protein. Such systems are well known in the art and are well within the realm of ordinary skill.
Another embodiment is a method for evaluating a test agent for inhibition of expression of an essential gene identified according to the methods herein, comprising:

    
    
        a) contacting a cell expressing said essential gene with said agent; and
        b) determining the amount or level of expression of said essential gene in said sample.
    
    


The exact determination method will be expected to vary depending on the characteristics of the expression product as would be readily apparent to one of ordinary skill in the art. Such methods can include, for example, antibody binding methods, enzymatic activity determinations, and substrate analog binding assays. Such level of expression could be monitored by monitoring the level of the product of the essential gene in the cell, i.e., by SDS-PAGE, or by calorimetric assays using, for example, a lacZ gene or protein fusion and detection on media using X-Gal or spectrophotometric detection.
When such fusions are employed, fusions may be designed using the chromosomal gene so long as the fusion does not disrupt the function of the essential gene, i.e., as with a gene fusion where lacZ is inserted just downstream of the essential gene and is expressed from the same promoter as the essential gene. Alternatively, one could employ an extrachromosomal fusion construct whereby the wild type chromosomal copy of the gene is not disrupted. In this case, one could employ a protein fusion, i.e., where a portion of lacZ sufficient to be detected with a colorimetric test is fused in frame with the coding region of the essential gene such that a fusion protein is obtained. Other detectable or measurable proteins commonly used in the art may be used as an alternative to lacZ, for instance, phoA, Lux/luciferase, etc.
Another method of the invention for evaluating an potential antibacterial agent, comprises the steps of:

    
    
        a) providing a bacterial strain comprising a mutant or normal form of the essential or important gene, wherein said mutant form of the gene confers a growth conditional phenotype;
        b) contacting bacteria of said bacterial strain with a test compound in semi-permissive or permissive growth conditions; and
        c) determining whether the growth of said bacterial strain comprising said mutant form of a gene is reduced in the presence of said test compound to a greater extent than a comparison bacteria comprising a normal form of said gene.
    
    


In this context, a “mutant form” of a gene is a gene which has been altered, either naturally or artificially, changing the base sequence of the gene, which results in a change in the amino acid sequence of an encoded polypeptide. The change in the base sequence may be of several different types, including changes of one or more bases for different bases, small deletions, and small insertions. Mutations may also include transposon insertions that lead to attenuated activity, i.e., by resulting in expression of a truncated protein. By contrast, a normal form of a gene is a form commonly found in a natural population of a bacterial strain. Commonly a single form of a gene will predominate in natural populations. In general, such a gene is suitable as a normal form of a gene, however, other forms which provide similar functional characteristics may also be used as a normal gene. In particular, a normal form of a gene does not confer a growth conditional phenotype on the bacterial strain having that gene, while a mutant form of a gene suitable for use in these methods does provide such a growth conditional phenotype.
As used in the present disclosure, the term “growth conditional phenotype” indicates that a bacterial strain having such a phenotype exhibits a significantly greater difference in growth rates in response to a change in one or more of the culture parameters than an otherwise similar strain not having a growth conditional phenotype. Typically, a growth conditional phenotype is described with respect to a single growth culture parameter, such as temperature. Thus, a temperature (or heat-sensitive) mutant (i.e., a bacterial strain having a heat-sensitive phenotype) exhibits significantly reduced growth, and preferably no growth, under non-permissive temperature conditions as compared to growth under permissive conditions. In addition, such mutants preferably also show intermediate growth rates at intermediate, or semi-permissive, temperatures. Similar responses also result from the appropriate growth changes for other types of growth conditional phenotypes. A growth conditional phenotype can also be conferred by cloning an essential or important gene behind a regulatable promoter, for instance, a promoter that is only active, or only leads to transcription, under particular environmental conditions or in response to a specific environmental stimulus. Such growth conditional promoter mutants may be isolated according to the promoter swap strategies described herein.
“Semi-permissive conditions” are conditions in which the relevant culture parameter for a particular growth conditional phenotype is intermediate between permissive conditions and non-permissive conditions. Consequently, in semi-permissive conditions the bacteria having a growth conditional phenotype will exhibit growth rates intermediate between those shown in permissive conditions and non-permissive conditions. In general, such intermediate growth rate is due to a mutant cellular component which is partially functional under semi-permissive conditions, essentially fully functional under permissive conditions, and is non-functional or has very low function under non-permissive conditions, where the level of function of that component is related to the growth rate of the bacteria.
The term “method of screening” means that the method is suitable, and is typically used, for testing for a particular property or effect in a large number of compounds. Therefore, the method requires only a small amount of time for each compound tested; typically more than one compound may be tested simultaneously (as in a 96-well microtiter plate, or in a series of replica plates), and preferably significant portions of the procedure can be automated. “Method of screening” also refers to determining a set of different properties or effects of one compound simultaneously.
Because the essential and important genes identified herein can be readily isolated and the genes cloned into a variety of vectors known in the art, the invention also encompasses vectors comprising the nucleic acid sequences, open reading frames and genes of the invention, as well as host cells containing such vectors. Because the essential genes identified herein can be readily isolated and the encoded gene products expressed by routine methods, the invention also provides the polypeptides encoded by those genes, as well as genes having at least about 50%, or more preferably about 60%, or more preferably about 70%, or more preferably about 80%, or more preferably about 90%, or most preferably about 95% protein sequence identity.
Thus, by identifying certain essential and/or important genes, this invention provides a method of screening for an antibacterial agent by contacting a polypeptide encoded by one of the identified essential or important genes, or a biologically active fragment of such a polypeptide, with a test compound, and determining whether the test compound binds to the polypeptide or polypeptide fragment. In addition, to simple binding determinations, the invention provides a method for identifying or evaluating an agent active on one of the identified essential genes. The method involves contacting a sample containing an expression product of one of the identified genes with the known or potential agent, and determining the amount or level of activity of the expression product in the sample.
In particular, antibodies to essential and important gene products are anticipated to be suitable diagnostic binding and antibacterial agents. Thus, antibodies to the proteins encoded by the essential and important genes identified by the methods described herein are also included in the invention. Such antibodies may be isolated according to well known techniques in the art, i.e., Kohler and Milstein for monoclonal antibodies. Also included are polyclonal antibodies and antibody fragments such as Fv, Fab and Fab2 fragments, as well as chimeric and humanized antibodies, and human antibodies, i.e., made using a Xeno mouse.
In a further aspect, this invention provides a method of diagnosing the presence of a bacterial strain having one of the genes identified above, by probing with an oligonucleotide at least 15 nucleotides in length, which specifically hybridizes to a nucleotide sequence which is the same as or complementary to the sequence of one of the bacterial genes identified above. In some cases, it is practical to detect the presence of a particular bacterial strain by direct hybridization of a labeled oligonucleotide to the particular gene. In other cases, it is preferable to first amplify the gene or a portion of the gene before hybridizing labeled oligonucleotides to those amplified copies.
In a related aspect, this invention provides a method of diagnosing the presence of a bacterial strain by specifically detecting the presence of the transcriptional or translational product of the gene. Typically, a transcriptional (RNA) product is detected by hybridizing a labeled RNA or DNA probe to the transcript. Detection of a specific translational (protein) product can be performed by a variety of different tests depending on the specific protein product. Examples would be binding of the product by specific labeled antibodies and, in some cases, detection of a specific reaction involving the protein product. Diagnostic assays find particular use in assaying tissue and fluid samples of patients suspect of having a Pseudomnonas infection.
Antibacterial agents identified according to the methods of the invention may be employed in pharmaceutical compositions. Such compositions may be administered to patients in order to treat an infection by or involving P. aeruginosa, either alone or in combination with secondary agents targeted at, for instance virulence factors of P. aeruginosa, or other bacteria that may be present in addition to P. aeruginosa. In this context, the term “administration” or “administering” refers to a method of giving a dosage of an antibacterial pharmaceutical composition to a mammal, where the method is, e.g., topical, oral, intranasal, inhaled, intravenous, transdermal, intraperitoneal, or intramuscular. The preferred method of administration can vary depending on various factors, e.g., the components of the pharmaceutical composition, the site of the potential or actual bacterial infection, the bacterium involved, and the severity of an actual bacterial infection.
As used above and throughout this application, “hybridize” has its usual meaning from molecular biology. It refers to the formation of a base-paired interaction between nucleotide polymers. The presence of base pairing implies that at least an appreciable fraction of the nucleotides in each of two nucleotide sequences are complementary to the other according to the usual base pairing rules. The exact fraction of the nucleotides which must be complementary in order to obtain stable hybridization will vary with a number of factors, including nucleotide sequence, salt concentration of the solution, temperature, and pH.
The term, “DNA molecule”, should be understood to refer to a linear polymer of deoxyribonucleotides, as well as to the linear polymer, base-paired with its complementary strand, forming double-strand DNA (dsDNA). The term is used as equivalent to “DNA chain” or “a DNA” or “DNA polymer” or “DNA sequence”, so this description of the term meaning applies to those terms also. The term does not necessarily imply that the specified “DNA molecule” is a discrete entity with no bonding with other entities. The specified DNA molecule may have H-bonding interactions with other DNA molecules, as well as a variety of interactions with other molecules, including RNA molecules. In addition, the specified DNA molecule may be covalently linked in a longer DNA chain at one, or both ends. Any such DNA molecule can be identified in a variety of ways, including, by its particular nucleotide sequence, by its ability to base pair under stringent conditions with another DNA or RNA molecule having a specified sequence, or by a method of isolation which includes hybridization under stringent conditions with another DNA or RNA molecule having a specified sequence.
References to a “portion” of a DNA or RNA chain mean a linear chain which has a nucleotide sequence which is the same as a sequential subset of the sequence of the chain to which the portion refers. Such a subset may contain all of the sequence of the primary chain or may contain only a shorter sequence. The subset will contain at least 15 bases in a single strand. However, by “same” is meant “substantially the same”; deletions, additions, or substitutions of specific nucleotides of the sequence, or a combination of these changes, which affect a small percentage of the full sequence will still leave the sequences substantially the same. Preferably this percentage of change will be less than 20%, more preferably less than 10%, and even more preferably less than 3%. “Same” is therefore distinguished from “identical”; for identical sequences there cannot be any difference in nucleotide sequences.
As used in reference to nucleotide sequences, “complementary” has its usual meaning from molecular biology. Two nucleotide sequences or strands are complementary if they have sequences that would allow base pairing between the strands according to the usual pairing rules. This does not require that the strands would necessarily base pair at every nucleotide; two sequences can still be complementary with a low level of base mismatch such as that created by deletion, addition, or substitution of one or a few (up to 5 in a linear chain of 25 bases) nucleotides, or a combination of such changes.
Other embodiments of the invention will be immediately envisaged by those of skill in the art upon reading the methods and examples to follow. Such examples are merely illustrative of the invention, and should not be construed as limiting the scope of the invention in any way.
Methodology
Generation of Transposon Library
Transposon insertions were generated using an improved transposon system for P. aeruginosa that utilizes a mini-Tn5-type transposon on a delivery vector that does not replicate in Pseudomonas. The delivery vector contains a modified transposase gene with three amino acid substitutions that have been shown to increase the frequency of Tn5 insertions. Weinreich et al., 1994, Evidence that cis preference of the Tn5 transposase is caused by nonproductive multimerizatior, Genes Dev. 8(19): 2363-74. The Tn5 transposase was placed under control of a lac promoter and the complete transposable element was minimized to 1.7 kilobases in length, including a tetracycline resistance marker and transcription terminator to prevent read-through into the genome. The transposon vector is delivered to P. aeruginosa via conjugation from a suitable E. coli host (e.g. SM10λpir). Following conjugation, transposon mutant are selected by resistance to tetracycline conferred by the trasnposable element.
Libraries were created in both P. aeruginosa PAK and PA01. The average diversity of the libraries created using this strategy is estimated to be  ̃40,000 to  ̃50,000 independent mutants per conjugation. Care is taken to minimize passage of each transposon conjugation before plating for mutant selection in an effort to minimize the potential for siblings, i.e., by stopping the conjugation after sufficient time for a single round of conjugation events.
High-Throughput Transposon Insertion Mapping (HTTIM)
Precise transposon insertion sites were determined by an anchored, semi-random PCR method for amplification of the transposase/genome junction region. O'Toole and Kolter, 1998, Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceeds via multiple, convergent signaling pathways: a genetic analysis, Mol. Microbiol. 28(3): 449-61. The technique, HTTIM, uses both Tn5 specific and semi-random primers with conserved primer tails. A small aliquot of transposon mutant liquid culture is used as a template and amplification of a fragment containing an insertion site is achieved in a two-step process. The PCR product is then sequenced and the insertion site is entered into an Oracle database for analysis. To date, more than 10,000 to 14,000 insertions have been mapped, each insertion representing the disruption of a gene or intergenic region that is not essential for survival on rich media.
With every insertion added to the map, the regions of the genome containing essential genes, and particularly those containing operons containing essential genes (because of potential polar effects of insertions in upstream genes), begin to become apparent because these regions will not be able to accommodate transposon insertions. Table 1 shows a listing of the open reading frames identified as existing between transposon insertions, as well as an indication of whether the gene has homologues that have been identified in other bacteria pursuant to BLAST sequence database analysis. Open reading frames were tentatively assigned names prior to being identified pursuant to HTTIM analysis, as disclosed in the Pseudomonas genome project, and reported in Stover et al., Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen, Aug. 21, 2000, Nature 406: 959-964, herein incorporated by reference in its entirety. For instance, the predicted ORFs were examined individually for (1) identity with known genes of P. aeruginosa with sequences deposited in GenBank, (2) similarity with well-characterized genes from other bacteria, or (3) presence of known functional motifs. In each case the literature was searched to ensure that the proteins encoded by the homologous genes were functionally characterized to avoid the perpetuation of poorly supported functional assignments. In addition, 61 researchers who were members of the P. aeruginosa research community or had experience in particular aspects of bacterial physiology were enlisted for the Pseudomonas Community Annotation Project (PseudoCAP) to provide expert assistance and confirmatory information in the genome project for the analysis of identified ORFs and assigned functions.
The genome project was able to assign a functional class to 54.2% of ORFs. As in other bacterial genomes, a large proportion of the genome (45.8% of ORFs) consists of genes for which no function could be determined or proposed (confidence level 4). Of these, nearly a third (769 ORFs) possess homology to genes of unknown function predicted in other bacterial genomes, and the remainder (32% of ORFs) do not have strong homology with any reported sequence. The 372 ORFs from the entire genome analysis that are known P. aeruginosa genes with demonstrated functions (confidence level 1) are primarily genes encoding lipopolysaccharide biosynthetic enzymes, virulence factors, such as exoenzymes and the systems that secrete them, and proteins involved in motility and adhesion. ORFs with strong homology to genes in other organisms with demonstrated functions (confidence level 2; 1,059 ORFs) include those required for DNA replication, protein synthesis, cell-wall biosynthesis and intermediary metabolism.
The ORFs that provided the most new information about P. aeruginosa biology via the genome annotation were those that could be assigned a probable function on the basis of similarity to established sequence motifs, but could not be assigned a definite name (confidence level 3; 1,590 ORFs). Most of these genes encode products that are in one of three functional classes: putative enzymes (405 genes), transcriptional regulators (341 genes) or transporters of small molecules (408 genes). In some cases genomic context provided additional information, allowing us to identify loci that appear to encode systems such as metabolic pathways and secretion systems, although the substrates for such systems could not be identified. The system for assigning name and putative function to each essential or important gene was gleaned from the Pseudomonas genome project data already available.
Statistical Analysis of Putative Essential and Important Genes
The open reading frames listed in Table 1 are also presented in Table 2, wherein the ORFs are listed in order of length of base pairs from longest to shortest. Also listed in Table 2 is the probability of essentiality assigned to each of the open reading frames. Probability correlates with length of the ORF, such that the longer the ORF, the higher the probability of hitting the ORF in a random transposon mutagenesis experiment, and the higher the confidence level that the ORF represents an essential or an important gene given that no transposon insertions therein were isolated. Statistical confidence levels in essentiality or importance can help narrow the focus in the screening of specific genes, thereby shortening the verification process and the, subsequent identification of antibacterial agents specific for that gene or gene product. Thus, one of the benefits of the HTTIM approach is that it is a quantitative approach that lends itself well to statistical analysis.
The High-Throughput Transposon Insertion Mapping (HTTIM) strategy utilizes a transposon, which is a small, mobile DNA element that randomly inserts into the chromosome. Although HTTIM was performed using a TnS transposon, any transposon may be employed so long as its insertion into the chromosome is random, i.e., devoid of hot spots. Reznikoff, W. S., 1993, The Tn5 transposon, Annu. Rev. Microbiol. 47: 945-63. Although the Tn5 derivative employed here contained a modified transposase gene with three amino acid substitutions that have been shown to increase the frequency of Tn5 insertions (see supra), the frequency of insertion is generally quite low. For instance, mutants with even one insertion occur at a rate of only 1 in 105 or 106 bacteria, and must be specifically selected from a background of cells with no insertions. Because the frequency of a single insertion is so low, the frequency of a double insertion is so low as to be insignificant.
When the transposon insertion disrupts one of the 5570 genes in the Pseudomonas genome, the function of that gene is lost. If the disrupted gene is essential for growth, the transposon insertion mutant dies and cannot be characterized. If the transposon disrupts a gene that is non-essential, the mutant survives, grows and the transposon insertion site is mapped. By examining the insertion sites of a large number of transposon mutants, all, of the non-essential P. aeruginosa genes can be identified, and by implication, all of the essential genes maybe identified as well. Characterization of over 13,000 transposon insertions revealed insertions in 3890 genes and resulted in an even distribution of insertions across the entire length of the genome. The remaining 1658 genes, in which a transposon insertion has never been observed, are candidates of essential genes (30%). See FIG. 7, showing a graph illustrating ORF coverage by Tn5 achieved in High-Throughput Transposon Insertion Mapping (HTTIM), wherein 30% of the genes in the genome are candidate essential genes where ORF size is not taken into account in predicting essentiality.
Because insertion of the transposon used here into the chromosome was. proposed to be random, it was possible that some of the 1658 genes that did not receive a transposon insertion were simply not hit by random chance. One cannot truly know that a transposon has no hot spots and is entirely random until the data is analyzed, and the data here confirmed that the Tn5 derivative employed underwent random insertion in P. aeruginosa. Thus, the chance that a gene will not be hit by the transposon as a matter of random chance increases as the length of the gene decreases, particularly for very small genes (<600 base pairs). See FIG. 8, Probability of Being an Essential Gene Given No Hit. Thus, by deleting smaller ORFs (<600 base pairs) in which there is a lower confidence in essentiality, the probability of essentiality goes up while the number of predicted essential genes decreases. Further, the curve in the graph depicted in FIG. 8 should level off faster. Thus, in predicting the essentiality of genes from the HTTIM candidate set, the closer one can come to a probability of 1.0 as depicted in FIG. 8, the higher the confidence level of essentiality that can be assigned to each gene in the candidate subset. For a representation of the number of ORFs of various lengths in P. aeruginosa, see the histogram in FIG. 9.
A Bayessian statistical model for truncated counting data was applied to the candidate essential gene set, and permitted a determination that 16 to 17 percent of P. aeruginosa genes are essential. Such a model may therefore be utilized to increase the statistical confidence that a given gene in the candidate subset is essential. An exemplary statistical model is provided in Example 1.
Physical Methods for Target Gene Validation
While the above methodology and the database of putative essential and important gene candidates established thereby is believed to be superior to existing methods with regard to the quantity of experimentation required to identify essential and important genes in Pseudomonas aeruginosa and the degree of confidence conferred, it should be understood that the methodology described herein can be incorporated into combined protocols with technology known in the art. For instance, the methods for verifying essentiality disclose in WO 01/07651, herein incorporated by reference in its entirety, would be useful as a secondary method to be utilized in combination with the methods described in this disclosure. Alternatively or additionally, one of several approaches may be used to determine whether a particular gene is essential (absolutely required for survival on rich medium) or important (the absence of which results in attenuated growth) to P. aeruginosa. 
Integration Knockouts
This is the simplest and most rapid strategy. PCR is used to amplify a small (200-500 base pairs) portion of the coding sequence, or open reading frame (ORF) of the gene of interest. This gene fragment must be centrally located within the ORF—it cannot include either termini of the gene's coding region. This fragment is cloned into a plasmid vector that can replicate in E. coli, but not in Pseudomonas. The vector used should have a drug resistance marker that is suitable for selection in Pseudomonas, and an origin for conjugal transfer. This feature allows the plasmid to be transferred by conjugation from a suitable E. coli donor strain to a Pseudomonas strain when the two are co-cultured under the appropriate conditions.
Following conjugation the co-cultured mixture is harvested and plated on media which selects against the E. coli donor and for Pseudomonas which contain the plasmid. Since the plasmid is incapable of extra-chromosomal replication in Pseudomonas, colonies that arise are the result of homologous recombination between the Pseudomonas chromosome and the cloned gene fragment on the plasmid. This is referred to as single-crossover recombination; a single recombination event takes place between the plasmid and the chromosome. The result is integration of the plasmid into the bacterial chromosome and disruption of the gene from which the fragment was amplified (FIG. 1).
Variations of this approach are possible. For instance, one could clone out the entire locus and isolate transposon insertion mutants in E.coli using known techniques, i.e., by transposition from the E. coli genome, selecting plasmid insertions by mobilizing the vector into a recipient cell that does not contain the transposon or the antibiotic resistance marker encoded by the transposon, and screening the plasmid for insertions in the cloned gene. Thereafter, a similar assay could be performed by screening for double crossover events in P. aeruginosa that result in recombination of the transposon into the chromosomal locus from a suicide vector.
Integration of the plasmid or other insertion at the locus can be confirmed by a relatively rapid PCR-based screen of recombinant colonies. The advantage of this strategy, particularly the plasmid single crossover strategy, is that it requires only amplification of a short stretch of DNA followed by a single cloning step before recombination experiments can be performed. The disadvantage is that if the target gene is essential, no recombinants can be obtained. Failure to obtain recombinants as proof of essentiality is pretty thin evidence. However, if a gene is in fact non-essential, this method will demonstrate that quickly.
Integration Knockouts with Extra-chromosomal Complementation
This variation of the above method provides more convincing data when the target gene is essential. It employs the same type of non-replicating integration plasmid described above, but recombinations are performed in strains already carrying a second copy of the target gene on an extra-chromosomal plasmid. This second copy can then supply the essential function when the chromosomal copy is disrupted. If disruptions can only be obtained when a complementing plasmid is present and not when a control plasmid is present, this is rather strong evidence that the target gene is essential. The advantage of this method is that you obtain colonies even when your gene is essential. The disadvantage is that construction and sequencing of the complementation plasmid takes additional time.
Integration with a Regulatable Promoter (Promoter Swap)
This approach also involves selecting for chromosomal integration of non-replicating plasmids via homologous recombination. However, the design of the integrating plasmid is different In this case, the N-terminal coding sequence (300-500 base pairs) of the target gene is PCR amplified and cloned into a vector downstream of a regulatable promoter, i.e., a lac promoter, which is inducible in the presence of IPTG, or an arabinose promoter (pABD), inducible in the presence of arabinose. The activity of the promoter can be modulated by the presence of a specific inducer molecule. The plasmid is conjugated into Pseudomonas and integration selected for under conditions where the regulatable promoter is active. The resulting chromosomal integration replaces the target gene's natural promoter with the regulatable promoter from the plasmid (FIG. 2). If the target gene is essential, recombinants can only survive when the inducer molecule is present in their growth media to stimulate gene expression. If the gene is non-essential, the recombinant's growth is independent of the addition of the inducer. The advantage of this strategy is that it requires only amplification of a short stretch of DNA followed by a single cloning step before recombination experiments can be performed.
EXAMPLES
Essential Genes Identified
Example 1
A Bayessian Statistical Model for Increasing Statistical Confidence of Essentiality
When the Tn5 transposon inserts into the Pseudomonas DNA, one of three things happen: 1) The insertion disrupts a nonessential gene. The cell survives to be characterized and the location of the insertion is determined. 2) The insertion disrupts an essential gene. The cell does not survive and the insertion site is not determined. 3) The insertion is in an intergenic region (between genes) and no information is gained. Genes with identified insertions are nonessential genes. However, genes without identified insertions could be essential genes or nonessential genes with zero transposon insertion. To determine the number of essential genes, we have developed a multivariate Bayession model for truncated Poisson data and applied it to the Pseudomonas genome data set. A likelihood gain based searching algorithm was developed to obtain maximum likelihood estimates. The property of the algorithm was studied Different approaches were compared for both multivariate and univariate approaches.
A. Structure of the Data and Preliminary Considerations
A transposon Tn5 insertion mutagenesis library was constructed in Pseudomonas aeruginosa strains PAK and PAO1. Mutants were randomly picked and their genomic insertion site sequence determined through polymerase chain reaction (PCR) and automated DNA sequencing. BLASTN analysis of transposon/genome junction sequences was used to map the location of the insertions relative to the completed strain PAO1 genome sequence. More than 20,000 mutants were analyzed which resulted in 12,219 independent insertions being mapped. In order to identify essential genes, transposon insertion sites were analyzed with respect to the protein-encoding genes in this organism A data set consists of the ID of genes, their length in DNA base-pairs, and the number of transposon insertions were obtained from experiments. The data set consists of 5570 genes with 881 different sizes ranging from 72 to 16884 DNA base-pairs. The distribution of the gene sizes are extremely skewed to the right with majority of the genes being smaller than 2000 DNA base-pairs as shown in FIG. 10.
A randomly selected subset of the data is shown in Table 4, where δ is gene size, x is the observed number of transposon insertions. Insertions to essential genes are not observable since the insertion mutants can not survive for characterization when the transposon is inserted into an essential gene. Therefore, a gene with zero observed transposon insertions can either be an essential gene or a nonessential gene with zero transposon insertion. Consequently, the count of transposon insertions x is truncated with the truncation region being a single element {0}.







TABLE 4







A sample of the gene data set









Gene id
δ
x












298
1359
3


4047
618
0


1170
735
1


4953
1044
1


5526
213
0


4624
1707
4


5069
426
3









Since the insertion into the chromosome of Pseudomonas aeruginosa is random (Reznikoff W S. 1993), and the probability of receiving an insertion for a given gene is proportional to its size measured in DNA base-pairs, the number of transposon insertions into a gene is distributed as truncated Poisson with parameter λδ, where δ is the size of the gene and λ is an unknown parameter, which is independent of gene size.
B. A Bayessian Model
Let R be a measurable subset of the probability space Ω such that a random variable X is observable only if X∈Ω\R. In this example, no observations can be obtained from essential genes, whereas only nonzero observations can be obtained from nonessential genes, the set R consists of a single element {0}.
1.
a. One Gene Size
Assume all genes in a genome have same size, δ, and let N be the number of nonessential genes in this genome. Then the observations X1, X2, . . . , XN from the N nonessential genes are i.i.d. Poisson(λ·δ), of which, all observations of value zero are truncated. The product λ·δ indicates that the probability of a gene receiving an insertion is proportional to its size.
Let {X1*,X2*, . . . ,Xn*}⊂{X1,X2, . . . ,XN} denote the subset of all nonzero observations. Then this subset composes a random sample of size n from a truncated Poisson distribution whose distribution function can be written as




  
    
      
        
          
            f
            ⁡
            
              (
              
                x
                ,
                
                  λ
                  ·
                  δ
                
              
              )
            
          
          =
          
            
              e
              
                
                  -
                  λ
                
                ·
                δ
              
            
            ⁢
            
              
                
                  (
                  
                    λ
                    ·
                    δ
                  
                  )
                
                x
              
              
                x
                !
              
            
            ⁢
            
              /
            
            ⁢
            
              (
              
                1
                -
                
                  e
                  
                    
                      -
                      λ
                    
                    ·
                    δ
                  
                
              
              )
            
          
        
        ,
        
          
        
        ⁢
        
          x
          =
          1
        
        ,
        2
        ,
        ...
      
    
    
      
        (
        3.1
        )
      
    
  




Let q=1−e−λ·δ denote the probability that an observation from Poisson(λ·δ) is not truncated, and let p=1−q≈e−λ·δ. Then, conditional on the parameters n and N, the likelihood function of the joint distribution of {X1*,X2*, . . . ,Xn*} can be written as




  
    
      
        
          L
          ⁡
          
            (
            
              
                λ
                |
                n
              
              ,
              N
            
            )
          
        
        =
        
          
            
              (
              
                λ
                ·
                δ
              
              )
            
            
              
                
              
              ⁢
              
                
                  ∑
                  
                    i
                    =
                    1
                  
                  n
                
                ⁢
                
                  
                
                ⁢
                
                  X
                  l
                  *
                
              
            
          
          ⁢
          
            
              (
              
                p
                q
              
              )
            
            n
          
          ⁢
          
            
              
                (
                
                  
                    ∏
                    
                      i
                      =
                      1
                    
                    n
                  
                  ⁢
                  
                    
                      X
                      i
                      *
                    
                    !
                  
                
                )
              
              
                -
                1
              
            
            .
          
        
      
    
    
      
        (
        3.2
        )
      
    
  




Let S=X1*+X2*+ . . . +Xn*  (3.3)

denote the sum of all nonzero observations and notice that n follows a binomial distribution B(N, q). The likelihood function of the joint distribution of {n,X1*,X2*, . . .,Xn*}, conditional on the parameter N, can be obtained as




  
    
      
        
          
            
              
                L
                ⁡
                
                  (
                  
                    λ
                    |
                    N
                  
                  )
                
              
              =
              
              ⁢
              
                
                  (
                  
                    
                      
                        N
                      
                    
                    
                      
                        n
                      
                    
                  
                  )
                
                ⁢
                
                  q
                  n
                
                ⁢
                
                  
                    
                      p
                      
                        N
                        -
                        n
                      
                    
                    ⁡
                    
                      (
                      
                        λ
                        ·
                        δ
                      
                      )
                    
                  
                  S
                
                ⁢
                
                  
                    (
                    
                      p
                      q
                    
                    )
                  
                  n
                
                ⁢
                
                  
                    (
                    
                      
                        ∏
                        
                          i
                          =
                          1
                        
                        n
                      
                      ⁢
                      
                        
                          X
                          i
                          *
                        
                        !
                      
                    
                    )
                  
                  
                    -
                    1
                  
                
              
            
          
        
        
          
            
              ∝
              
              ⁢
              
                
                  (
                  
                    
                      
                        N
                      
                    
                    
                      
                        n
                      
                    
                  
                  )
                
                ⁢
                
                  λ
                  s
                
                ⁢
                
                  
                    e
                    
                      
                        -
                        
                          (
                          
                            λ
                            ·
                            δ
                          
                          )
                        
                      
                      ⁢
                      N
                    
                  
                  .
                
              
            
          
        
      
    
    
      
        (
        3.4
        )
      
    
  




The Bayesian model consists of the conditional model (2.4) and a prior distribution of the parameter N. Assuming N, the number of nonessential genes, is binomial B(M, γ), where M is the total number of genes of size δ, which is known, and γ is the portion of nonessential genes which is unknown and is independent of gene size, we can write the likelihood function of the joint distribution of {n,N,X1*,X2*, . . . ,Xn*} as




  
    
      
        
          L
          ⁡
          
            (
            
              γ
              ,
              λ
              ,
              N
            
            )
          
        
        ∝
        
          
            (
            
              
                
                  M
                
              
              
                
                  N
                
              
            
            )
          
          ⁢
          
            (
            
              
                
                  N
                
              
              
                
                  n
                
              
            
            )
          
          ⁢
          
            
              
                γ
                N
              
              ⁡
              
                (
                
                  1
                  -
                  γ
                
                )
              
            
            
              M
              -
              N
            
          
          ⁢
          
            λ
            s
          
          ⁢
          
            
              e
              
                
                  -
                  
                    (
                    
                      λ
                      ·
                      δ
                    
                    )
                  
                
                ⁢
                N
              
            
            .
          
        
      
    
    
      
        (
        3.5
        )
      
    
  




This is the likelihood function of n nonzero observations from M genes of the same size δ, of which N genes are nonessential. It is easy to see that (3.5) is proportional to the likelihood function of the posterior distribution of N given observations n and S.
2.
b. Multiple Gene Sizes
For a given genome consists of genes of different sizes, let {right arrow over (δ)}=(δ1,δ2, . . . ,δg)T denote the vector of g different gene sizes, and let {right arrow over (M)}=(M1,M2, . . . ,Mg)t the vector of known numbers of total genes, {right arrow over (N)}=(N1,N2, . . . ,Ng)T the unknown numbers of nonessential genes, {right arrow over (n)}=(n1,n2, . . . ,ng)T the numbers of nonzero observations from the nonessential genes, and {right arrow over (S)}=(S1,S2, . . . ,Sg)T the sums of nonzero observations, as defined in (3.3).
The likelihood function of the joint distribution of {{right arrow over (n)},{right arrow over (N)},{right arrow over (S)}} can be written as




  
    
      
        
          L
          ⁡
          
            (
            
              γ
              ,
              λ
              ,
              
                N
                →
              
            
            )
          
        
        ∝
        
          
            
              
                γ
                
                  
                  
                    N
                    →
                  
                  
                
              
              ⁡
              
                (
                
                  1
                  -
                  γ
                
                )
              
            
            
              
                
                
                  M
                  →
                
                
              
              -
              
                
                
                  N
                  →
                
                
              
            
          
          ⁢
          
            λ
            
              
              
                S
                →
              
              
            
          
          ⁢
          
            e
            
              
                -
                λ
              
              ·
              
                (
                
                  
                    
                      δ
                      →
                    
                    T
                  
                  ·
                  
                    N
                    _
                  
                
                )
              
            
          
          ⁢
          
            
              ∏
              
                i
                =
                1
              
              g
            
            ⁢
            
              
                (
                
                  
                    
                      
                        M
                        i
                      
                    
                  
                  
                    
                      
                        N
                        i
                      
                    
                  
                
                )
              
              ⁢
              
                (
                
                  
                    
                      
                        N
                        i
                      
                    
                  
                  
                    
                      
                        n
                        i
                      
                    
                  
                
                )
              
            
          
        
      
    
    
      
        (
        3.6
        )
      
    
  




where ∥*∥ is the L1 norm of a vector, and





  
    
      
        δ
        →
      
      T
    
    ·
    
      N
      →
    
  
  =
  
    
      ∑
      
        i
        =
        1
      
      g
    
    ⁢
    
      
        δ
        i
      
      ·
      
        
          N
          i
        
        .
      
    
  




Let I=ln(L). Then up to an additive constant, the log likelihood function of the joint distribution of {{right arrow over (n)},{right arrow over (N)},{right arrow over (S)}} can be written as




  
    
      
        
          
                        ⁢
            
              (
              
                γ
                ,
                λ
                ,
                
                  N
                  →
                
              
              )
            
          
          =
          
            
              
                
                
                  N
                  →
                
                
              
              ·
              
                ln
                ⁡
                
                  (
                  γ
                  )
                
              
            
            +
            
              
                (
                
                  
                    
                    
                      M
                      →
                    
                    
                  
                  -
                  
                    
                    
                      N
                      →
                    
                    
                  
                
                )
              
              ·
              
                ln
                ⁡
                
                  (
                  
                    1
                    -
                    γ
                  
                  )
                
              
            
            +
            
              
                
                
                  S
                  →
                
                
              
              ·
              
                ln
                ⁡
                
                  (
                  λ
                  )
                
              
            
            -
            
              λ
              ·
              
                (
                
                  
                    
                      δ
                      →
                    
                    T
                  
                  ·
                  
                    N
                    →
                  
                
                )
              
            
            -
            
              
                ∑
                
                  i
                  ⁢
                  
                    
                  
                  =
                  
                    
                  
                  ⁢
                  1
                
                
                  
                    
                  
                  ⁢
                  g
                
              
              ⁢
              
                ln
                ⁡
                
                  (
                  
                    
                      (
                      
                        
                          M
                          
                            
                              
                            
                            ⁢
                            i
                          
                        
                        -
                        
                          N
                          
                            
                              
                            
                            ⁢
                            i
                          
                        
                      
                      )
                    
                    !
                  
                  )
                
              
            
            -
            
              
                ∑
                
                  i
                  =
                  1
                
                g
              
              ⁢
              
                (
                
                  
                    (
                    
                      
                        N
                        i
                      
                      -
                      
                        n
                        i
                      
                    
                    )
                  
                  !
                
                )
              
            
          
        
        ,
      
    
    
      
        (
        3.7
        )
      
    
  




where (γ,λ,{right arrow over (N)}) are the parameters of interests. The vector {right arrow over (N)} is defined on {ni≦Ni≦Mi: i=1,2,. . . ,g} and I(γ,λ,{right arrow over (N)}) is proportional to the likelihood function of the posterior distribution of {right arrow over (N)} given {right arrow over (n)} and {right arrow over (S)}.

When g is large, say, in the order of hundreds as in the situation we are dealing with in this paper, obtaining the maximum likelihood (ML) estimate of {right arrow over (N)}=(N1,N2, . . . ,Ng)T from (3.7) in such a high dimensional parameter space is a very difficult task both theoretically and computationally. In the next section, we will present a stepwise, maximum likelihood gain based method to obtain the ML estimation.
C. ML Estimation of Parameters
For any {right arrow over (N)}=(N1,N2, . . . ,Ng)T, it is easy to verify using (3.7) that the ML estimations of the parameters γ and λ are

{circumflex over (γ)}=∥{right arrow over (N)}∥/∥{right arrow over (M)}∥  (4.1)

and

{circumflex over (λ)}=∥{right arrow over (S)}∥/({right arrow over (δ)}T·{right arrow over (N)})  (4.2)

respectively. Substituting (4.1) and (4.2) for γ and λ in (3.7), we have





  
    
      
        
          
                        *
          
          ⁢
          
            (
            
              N
              →
            
            )
          
        
        ∝
        
          
            
              
              
                N
                →
              
              
            
            ·
            
              ln
              ⁡
              
                (
                
                  
                  
                    N
                    →
                  
                  
                
                )
              
            
          
          +
          
            
              
                (
                
                  
                    
                    
                      M
                      →
                    
                    
                  
                  -
                  
                    
                    
                      N
                      →
                    
                    
                  
                
                )
              
              ·
              ln
            
            ⁢
            
              
            
            ⁢
            
              (
              
                
                  
                  
                    M
                    →
                  
                  
                
                -
                
                  
                  
                    N
                    →
                  
                  
                
              
              )
            
          
          -
          
            
              
              
                S
                →
              
              
            
            ·
            
              ln
              (
              
                
                  
                    δ
                    →
                  
                  T
                
                ·
                
                  N
                  →
                
              
              )
            
          
          -
          
            
              ∑
              
                i
                =
                1
              
              g
            
            ⁢
            
              
                (
                
                  
                    ln
                    ⁡
                    
                      (
                      
                        
                          (
                          
                            
                              M
                              i
                            
                            -
                            
                              N
                              i
                            
                          
                          )
                        
                        !
                      
                      )
                    
                  
                  +
                  
                    ln
                    ⁡
                    
                      (
                      
                        
                          (
                          
                            
                              N
                              i
                            
                            -
                            
                              n
                              i
                            
                          
                          )
                        
                        !
                      
                      )
                    
                  
                
                )
              
              .
            
          
        
      
    
    
      
        (
        4.3
        )
      
    
  




For 1≦i≦g, define

ΔiI*({right arrow over (N)})=I*({right arrow over (N)}+{right arrow over (1)}i)−I*({right arrow over (N)})  (4.4)

for any {right arrow over (N)}∈{ni≦Ni<Mi, nj≦Nj≦Mj: i≠j}. In equation (4.4), {right arrow over (1)}i=(0, . . . 0,1,0, . . . ,0)T with 1 at the ith position. For notational purpose, let

η(k)=k·ln(k)+(∥{right arrow over (M)}∥−k)·ln(∥{right arrow over (M)}−k)  (4.5)

for ∥{right arrow over (n)}∥≦k<∥{right arrow over (M)}∥. Then, (3.4) can be written as





  
    
      
        
          
            Δ
            i
          
          ⁢
          
                        *
          
          ⁢
          
            (
            
              N
              →
            
            )
          
        
        =
        
          
            η
            ⁡
            
              (
              
                
                  
                  
                    N
                    →
                  
                  
                
                +
                1
              
              )
            
          
          -
          
            η
            ⁡
            
              (
              
                
                
                  N
                  →
                
                
              
              )
            
          
          -
          
            
              
              
                S
                →
              
              
            
            ·
            
              ln
              ⁡
              
                (
                
                  1
                  +
                  
                    
                      
                        δ
                        i
                      
                      /
                      
                        
                          δ
                          →
                        
                        T
                      
                    
                    ·
                    
                      N
                      →
                    
                  
                
                )
              
            
          
          +
          
            
              ln
              ⁡
              
                (
                
                  
                    
                      M
                      i
                    
                    -
                    
                      N
                      i
                    
                  
                  
                    
                      N
                      i
                    
                    -
                    
                      n
                      i
                    
                    +
                    1
                  
                
                )
              
            
            .
          
        
      
    
    
      
        (
        4.6
        )
      
    
  




To obtain ML estimation of {right arrow over (N)}, we define an operator, ⊕, between the observed vector {right arrow over (n)} and any integer k with 0≦k≦∥{right arrow over (M)}∥−∥{right arrow over (n)}∥ as follows:

{right arrow over (n)}⊕0={right arrow over (n)}, 

{right arrow over (n)}⊕1={{right arrow over (n)}+{right arrow over (1)}i: ΔiI*({right arrow over (n)})≧ΔjI*({right arrow over (n)}) for all j≠i}, and

{right arrow over (n)}⊕k=({right arrow over (n)}⊕(k−1))⊕1 for k≧2.  (4.7)

We also define a likelihood-gain function G with G(0)=0 and

G(k)=I*({right arrow over (n)}⊕k)−I*({right arrow over (n)}⊕(k−1))  (4.8)

for 1≦k≦∥{right arrow over (M)}∥−∥{right arrow over (n)}∥.

Using this likelihood-gain function, we can search the ML estimation for {right arrow over (N)} as follows:

    1. Start with the observation {right arrow over (n)} as the initial estimate of {right arrow over (N)}, and denote it as {right arrow over (N)}0.
    2. For each gene size δi with ni<Mi, i=1, 2, . . . , g, calculate a likelihood difference ΔiI*({right arrow over (N)}0)=I*({right arrow over (N)}0+{right arrow over (1)}i)−I*({right arrow over (N)}0) by set Ni0=ni+1 and Nj0=ni for all j≠i.
    3. Update the initial values {right arrow over (N)}0 by setting Ni0=Ni0+1 such that ΔiI*({right arrow over (N)}0)=max{ΔjI*({right arrow over (N)}0), j=1,2, . . . ,g}. This maximum likelihood difference is the likelihood gain defined in (4.8).
    4. Repeat the process until it converges. By convergence we mean that either the estimated number of nonessential genes equals to the number of genes in each size group or when increasing the number of nonessential genes in any size groups will result in a loss of likelihood.


This algorithm searches the ML estimator in a high dimensional space (881 in our study) along a path such that at each iteration, it moves in a direction (that is, increases the number of nonessential genes in this size group by one) along which the likelihood gain is maximum among all possible directions. Because the searching algorithm prohibits reversal of previous moves at any later iteration, it moves towards the ML estimator along the shortest path with the deepest ascending (maximum likelihood gain) at each step. Table 5 and FIGS. 11 and 12 show the values of likelihood gains in each iteration. With very few exceptions where the monotonous is violated only at the fourth or fifth decimal places that probably can be attributed to rounding errors, the likelihood gain is a monotonously decreasing function.







TABLE 5







A Sample of Likelihood Gains at Each Iteration













Iteration
id
δ
M
n
{circumflex over (N)}(i)
G(i)
















1
28
210
13
2
3
2.67559


2
60
306
14
3
4
2.41082


3
44
258
14
5
6
2.34388


4
63
315
15
5
6
2.29243


. . .
. . .
. . .
. . .
. . .
. . .
. . .


18
32
222
7
1
2
2.05160


19
81
369
11
2
3
2.05166


. . .
. . .
. . .
. . .
. . .
. . .
. . .


774
122
492
12
8
11
0.00692


775
266
924
16
14
15
0.00544


776
85
381
14
3
11
0.00531









The following three theorems show that the estimates obtained through the above algorithm are indeed the maximum likelihood estimates.

Theorem 1: if





  
    
      
        
          
            
              ∑
              
                i
                =
                1
              
              g
            
            ⁢
            
              (
              
                
                  n
                  i
                
                -
                
                  exp
                  ⁡
                  
                    (
                    
                      
                        
                          δ
                          i
                        
                        ·
                        
                          
                          
                            S
                            →
                          
                          
                        
                      
                      
                        
                          
                            δ
                            →
                          
                          T
                        
                        ·
                        
                          n
                          →
                        
                      
                    
                    )
                  
                
              
              )
            
          
          >
          0
        
        ,
      
    
    
      
        (
        4.9
        )
      
    
  




then G(1)>0.

Proof: If G(1)≦0, then by (4.5), ΔiI*({right arrow over (n)})≦0 for all 1≦i≦g, which leads to

η(∥{right arrow over (n)}∥+1)−η(∥{right arrow over (n)}∥)−∥{right arrow over (S)}∥·in(1+δi/({right arrow over (δ)}T·{right arrow over (n)}))+ln(Mi−ni)≦0 




  
    
      
        ⇒
      
      
        
          
            
              
                
                  
                  
                    S
                    →
                  
                  
                
                ·
                i
              
              ⁢
              
                
              
              ⁢
              
                n
                (
                
                  1
                  +
                  
                    
                      δ
                      i
                    
                    /
                    
                      (
                      
                        
                          
                            δ
                            →
                          
                          T
                        
                        ·
                        
                          n
                          →
                        
                      
                      )
                    
                  
                
                )
              
            
            -
            
              ln
              ⁡
              
                (
                
                  
                    M
                    i
                  
                  -
                  
                    n
                    i
                  
                
                )
              
            
          
          ≥
          
            
              η
              ⁡
              
                (
                
                  
                    
                    
                      n
                      →
                    
                    
                  
                  +
                  1
                
                )
              
            
            -
            
              η
              ⁡
              
                (
                
                  
                  
                    n
                    →
                  
                  
                
                )
              
            
          
        
      
    
  




  
    
      
        ⇒
      
      
        
          
            
              
                (
                
                  1
                  +
                  
                    
                      δ
                      i
                    
                    /
                    
                      (
                      
                        
                          
                            δ
                            →
                          
                          T
                        
                        ·
                        
                          n
                          →
                        
                      
                      )
                    
                  
                
                )
              
              
                
                
                  S
                  →
                
                
              
            
            
              
                M
                i
              
              -
              
                n
                i
              
            
          
          ≥
          
            
              
                
                  (
                  
                    
                      
                      
                        n
                        →
                      
                      
                    
                    +
                    1
                  
                  )
                
                
                  
                    
                    
                      n
                      →
                    
                    
                  
                  +
                  1
                
              
              ·
              
                
                  (
                  
                    
                      
                      
                        M
                        →
                      
                      
                    
                    -
                    
                      
                      
                        n
                        →
                      
                      
                    
                    -
                    1
                  
                  )
                
                
                  
                    
                    
                      M
                      →
                    
                    
                  
                  -
                  
                    
                    
                      n
                      →
                    
                    
                  
                  -
                  1
                
              
            
            
              
                
                  (
                  
                    
                    
                      n
                      →
                    
                    
                  
                  )
                
                
                  
                    
                    
                      n
                      →
                    
                    
                  
                  +
                  1
                
              
              ·
              
                
                  (
                  
                    
                      
                      
                        M
                        →
                      
                      
                    
                    -
                    
                      
                      
                        n
                        →
                      
                      
                    
                  
                  )
                
                
                  
                    
                    
                      M
                      →
                    
                    
                  
                  -
                  
                    
                    
                      n
                      →
                    
                    
                  
                
              
            
          
        
      
    
  




  
    
      
        ⇒
      
      
        
          
            
              ∑
              
                l
                =
                1
              
              g
            
            ⁢
            
              
                (
                
                  1
                  +
                  
                    
                      δ
                      i
                    
                    /
                    
                      (
                      
                        
                          
                            δ
                            →
                          
                          T
                        
                        ·
                        
                          n
                          →
                        
                      
                      )
                    
                  
                
                )
              
              
                
                
                  S
                  →
                
                
              
            
          
          ≥
          
            
              
              
                n
                →
              
              
            
            ·
            
              
                (
                
                  1
                  +
                  
                    1
                    /
                    
                      
                      
                        n
                        →
                      
                      
                    
                  
                
                )
              
              
                
                  
                  
                    n
                    →
                  
                  
                
                +
                1
              
            
            ·
            
              

            
            ⁢
            
              
            
            ⁢
            
              
                (
                
                  1
                  +
                  
                    1
                    /
                    
                      (
                      
                        
                          
                          
                            M
                            →
                          
                          
                        
                        -
                        
                          
                          
                            n
                            →
                          
                          
                        
                      
                      )
                    
                  
                
                )
              
              
                
                  
                  
                    M
                    →
                  
                  
                
                -
                
                  
                  
                    n
                    →
                  
                  
                
                -
                1
              
            
          
        
      
    
  



Using the facts that (1+1/x)x<e, (1+1/x)x+1>e, and (1−1/x)x−1>e−1 for any x>0, we obtain





  
    
      
        ∑
        
          i
          =
          1
        
        g
      
      ⁢
      
        exp
        ⁡
        
          (
          
            
              
                δ
                i
              
              ·
              
                
                
                  S
                  →
                
                
              
            
            
              
                
                  δ
                  →
                
                T
              
              ·
              
                n
                →
              
            
          
          )
        
      
    
    ≥
    
      
        
        
          n
          →
        
        
      
      ·
      e
      ·
      
        e
        
          -
          1
        
      
    
  
  =
  
    
      
      
        n
        →
      
      
    
    ⁢
    
      

    
    ⇒
    
      
        
          ∑
          
            l
            =
            1
          
          g
        
        ⁢
        
          (
          
            
              n
              i
            
            -
            
              exp
              ⁡
              
                (
                
                  
                    
                      δ
                      i
                    
                    ·
                    
                      
                      
                        S
                        →
                      
                      
                    
                  
                  
                    
                      
                        δ
                        →
                      
                      T
                    
                    ·
                    
                      n
                      →
                    
                  
                
                )
              
            
          
          )
        
      
      <
      0
    
  




This is contradictory to condition (4.9).

For g=1, (4.9) becomes ln(n)>(X1+X2+ . . . +Xn)/n. Hence, when the mean of the observed transposon insertions is less than the log of the number of nonzero observations, the vector {right arrow over (n)} can not be the ML estimator of {right arrow over (N)} and there must be truncated observations from nonessential genes.

Theorem 2:

ΔiI*({right arrow over (N)})>ΔiI*({right arrow over (N)}−{right arrow over (1)}j) for all i≠j  (4.10)

Proof: By definition in (4.5),





  
    
      d
      
        [
        
          
            η
            ⁡
            
              (
              
                x
                +
                1
              
              )
            
          
          -
          
            η
            ⁡
            
              (
              x
              )
            
          
        
        ]
      
    
    
      d
      x
    
  
  =
  
    
      ln
      ⁡
      
        (
        
          
            
              x
              +
              1
            
            x
          
          ·
          
            
              
                
                
                  M
                  →
                
                
              
              -
              x
            
            
              
                
                
                  M
                  →
                
                
              
              -
              x
              -
              1
            
          
        
        )
      
    
    >
    0
  




for any 0<x<∥{right arrow over (M)}∥. Hence η(∥{right arrow over (N)}∥+1)−η(∥{right arrow over (N)}∥) is an increase function of ∥{right arrow over (N)}∥. Using this result, we have





  
    
      
        Δ
        i
      
      ⁢
      
                *
      
      ⁢
      
        (
        
          N
          →
        
        )
      
    
    -
    
      
        Δ
        i
      
      ⁢
      
        
          T
          *
        
        ⁡
        
          (
          
            
              N
              →
            
            -
            
              
                1
                →
              
              j
            
          
          )
        
      
    
  
  =
  
    
      
        (
        
          
            η
            ⁡
            
              (
              
                
                  
                  
                    N
                    →
                  
                  
                
                +
                1
              
              )
            
          
          -
          
            η
            ⁡
            
              (
              
                
                
                  N
                  →
                
                
              
              )
            
          
          -
          
            η
            ⁡
            
              (
              
                
                  
                  
                    N
                    →
                  
                  
                
                -
                1
              
              )
            
          
        
        )
      
      -
      
        
          
          
            S
            →
          
          
        
        ·
        
          ln
          ⁡
          
            (
            
              1
              +
              
                
                  δ
                  i
                
                /
                
                  (
                  
                    
                      
                        δ
                        →
                      
                      T
                    
                    ·
                    
                      N
                      →
                    
                  
                  )
                
              
            
            )
          
        
      
      +
      
        
          
          
            S
            →
          
          
        
        ·
        
          ln
          ⁡
          
            (
            
              1
              +
              
                
                  δ
                  i
                
                /
                
                  (
                  
                    
                      
                        
                          δ
                          →
                        
                        T
                      
                      ·
                      
                        N
                        →
                      
                    
                    -
                    
                      δ
                      j
                    
                  
                  )
                
              
            
            )
          
        
      
    
    >
    
      
        
        
          S
          →
        
        
      
      ·
      
        [
        
          
            ln
            ⁡
            
              (
              
                1
                +
                
                  
                    δ
                    i
                  
                  /
                  
                    (
                    
                      
                        
                          
                            δ
                            →
                          
                          i
                        
                        ·
                        
                          N
                          →
                        
                      
                      -
                      
                        σ
                        j
                      
                    
                    )
                  
                
              
              )
            
          
          -
          
            ln
            ⁡
            
              (
              
                1
                +
                
                  
                    δ
                    i
                  
                  /
                  
                    (
                    
                      
                        
                          δ
                          →
                        
                        T
                      
                      ·
                      
                        N
                        →
                      
                    
                    )
                  
                
              
              )
            
          
        
        ]
      
    
    >
    0
  




Theorem 3:

Under (4.9), for any 1≦j≦g and 1≦k≦K*, with K*=max{k*≧0: G(k)≧0 for all 0≦k≦k*}, if {right arrow over (N)}={right arrow over (n)}⊕k−{right arrow over (1)}j ∈{nj≦Nj≦Mj}, then

I*({right arrow over (n)}⊕k)>I*({right arrow over (n)}⊕k−{right arrow over (1)}j)  (4.11)

Proof: This is obviously true when k=1. Assume (3.11) is true for integers 1,2, . . . , k. For integer k+1, we have





  
    
      
                *
      
      ⁢
      
        (
        
          
            
              n
              →
            
            ⊕
            
              (
              
                k
                +
                1
              
              )
            
          
          -
          
            
              1
              →
            
            j
          
        
        )
      
    
    -
    
      
                *
      
      ⁢
      
        (
        
          
            n
            →
          
          ⊕
          k
        
        )
      
    
  
  =
  
    

  
  ⁢
  
    
      
        [
        
          
            
                            *
            
            ⁢
            
              (
              
                
                  
                    n
                    →
                  
                  ⊕
                  
                    (
                    
                      k
                      +
                      1
                    
                    )
                  
                
                -
                
                  
                    1
                    →
                  
                  j
                
              
              )
            
          
          -
          
            
                            *
            
            ⁢
            
              (
              
                
                  
                    n
                    →
                  
                  ⊕
                  k
                
                -
                
                  
                    1
                    →
                  
                  j
                
              
              )
            
          
        
        ]
      
      +
      
        

      
      ⁢
      
        
      
      ⁢
      
        [
        
          
            
                            *
            
            ⁢
            
              (
              
                
                  
                    n
                    →
                  
                  ⊕
                  k
                
                -
                
                  
                    1
                    →
                  
                  j
                
              
              )
            
          
          -
          
            
                            *
            
            ⁢
            
              (
              
                
                  n
                  →
                
                ⊕
                k
              
              )
            
          
        
        ]
      
    
    <
    
      

    
    ⁢
    
      
    
    ⁢
    
      [
      
        
          
                        *
          
          ⁢
          
            (
            
              
                
                  n
                  →
                
                ⊕
                
                  (
                  
                    k
                    +
                    1
                  
                  )
                
              
              -
              
                
                  1
                  →
                
                j
              
            
            )
          
        
        -
        
          
                        *
          
          ⁢
          
            (
            
              
                
                  n
                  →
                
                ⊕
                k
              
              -
              
                
                  1
                  →
                
                j
              
            
            )
          
        
      
      ]
    
  




By theorem 2,

I*({right arrow over (n)}⊕(k+1)−{right arrow over (1)}j)−I*({right arrow over (n)}⊕k−{right arrow over (1)}j)<I*({right arrow over (n)}⊕(k+1))−I*({right arrow over (n)}⊕k)

Therefore

I*({right arrow over (n)}⊕(k+1))>I*({right arrow over (n)}⊕(k+1)−{right arrow over (1)}j)

Combining theorems 1-3, we obtain

Theorem 4: If the likelihood function defined in (3.7) has an unique solution, the ML estimator of {right arrow over (N)} is:

{right arrow over ({circumflex over (N)}={right arrow over (n)}⊕K*  (4.12)

Theorem 3 guarantees that the trajectory of the searching algorithm follows the shortest path in the sense that a reversal of a previous move (that is, removal of a previously added nonessential gene of any gene size) at any later state will result in a loss of likelihood. This property is illustrated in FIG. 4 which shows the trajectory of the searching algorithm projected in a subspace spanned by two different gene sizes. For illustration purpose, genes are grouped into 143 groups by grouping genes with similar sizes together to increase the length of the trajectory. As indicated in the plot at any state, moving backwards in any direction results in a loss of likelihood. FIG. 13 shows more trajectories projected in different subspaces.
Now we need to demonstrate that the likelihood function (3.7), which is defined in a high dimensional discrete space, has an unique solution. This can be established if the same estimations are obtained from different initial values. Since the initial values can be any value between the observation {right arrow over (n)} and the total number of genes {right arrow over (M)}, we need to extend the searching algorithm (4.7) as follows:
For any initial value {{right arrow over (N)}0: ni≦Ni0<Mi for i=1,2, . . . , g} and any integer k with




  
    
      
        0
        ≤
        k
        ≤
        
          
            
            
              M
              →
            
            
          
          -
          
            
              
              
                
                  N
                  →
                
                0
              
              
            
            ⁢
            
              
            
            ⁢
            such
            ⁢
            
              
            
            ⁢
            that
            ⁢
            
              
            
            ⁢
            
              
                
                  
                    
                      
                        
                          
                            N
                            →
                          
                          0
                        
                        ⊕
                        0
                      
                      =
                      
                        
                          N
                          →
                        
                        0
                      
                    
                    ,
                  
                
              
              
                
                  
                    
                      
                        
                          
                            N
                            →
                          
                          0
                        
                        ⊕
                        1
                      
                      =
                      
                        {
                        
                          
                            
                              
                                N
                                →
                              
                              0
                            
                            ±
                            
                              1
                              i
                            
                          
                          :
                          
                            
                          
                          ⁢
                          
                            
                              
                                Δ
                                i
                              
                              ⁢
                              
                                                                *
                              
                              ⁢
                              
                                (
                                
                                  
                                    N
                                    →
                                  
                                  0
                                
                                )
                              
                            
                            ≥
                            
                              
                                Δ
                                j
                              
                              ⁢
                              
                                                                *
                              
                              ⁢
                              
                                (
                                
                                  
                                    N
                                    →
                                  
                                  0
                                
                                )
                              
                              ⁢
                              
                                
                              
                              ⁢
                              for
                              ⁢
                              
                                
                              
                              ⁢
                              all
                              ⁢
                              
                                
                              
                              ⁢
                              j
                            
                            ≠
                            i
                          
                        
                        }
                      
                    
                    ,
                    and
                  
                
              
              
                
                  
                    
                      
                        
                          N
                          →
                        
                        0
                      
                      ⊕
                      k
                    
                    =
                    
                      
                        
                          (
                          
                            
                              
                                N
                                →
                              
                              0
                            
                            ⊕
                            
                              (
                              
                                k
                                -
                                1
                              
                              )
                            
                          
                          )
                        
                        ⊕
                        
                          1
                          ⁢
                          
                            
                          
                          ⁢
                          for
                          ⁢
                          
                            
                          
                          ⁢
                          k
                        
                      
                      ≥
                      2.
                    
                  
                
              
            
          
        
      
    
    
      
        (
        4.13
        )
      
    
  




The likelihood gain function is extended similarly as G(0)=0 and

G(k)=I*({right arrow over (N)}0⊕k)−I*({right arrow over (N)}0⊕(k−1))  (4.14)

for 1≦k≦∥{right arrow over (M)}∥−∥{right arrow over (N)}0∥.

Algorithm (4.13) preserves all the properties of algorithm (4.7) and it searches the ML estimator the same way as that of algorithm (4.7) with two exceptions. Unlike algorithm (4.7), which uses {right arrow over (n)} as initial values of {right arrow over (N)} and at each iteration, the number of nonessential genes is increased by one in gene groups of size δi to find the maximum likelihood gain, this algorithm uses {right arrow over (N)}0 as initial values of {right arrow over (N)} which can be greater than the ML estimator. Therefore, at each iteration, the number of nonessential genes in a group with size δi can be either increased or decreased by one such that the likelihood gain is maximum.
Randomly selected initial values {right arrow over (N)}0 were used for data with grouped gene sizes and data with exact gene sizes. The estimations of all parameters are exactly the same and the final likelihood for all initial values {right arrow over (N)}0 are exactly the same as indicated in FIG. 14, which plots twenty seven different initial values of {right arrow over (N)}0. The line in the far left represents the likelihood when {right arrow over (N)}0={right arrow over (n)}, and the lines in the middle are randomly selected. FIG. 15 is the trajectory projected into a subspace spanned by two gene sizes. Each circle represents the projection of a different initial value {right arrow over (N)}0. Regardless of the initial values, the trajectories all converge to the ML estimator.
D. Analysis of Pseudomonas Aeruginosa Data


    1. Multivariate Model with Exact Gene Sizes


The data considered here consist of observations from 5570 genes in 881 different sizes, ranging from 72 to 16884 DNA base-pairs. Distribution of gene size is severely skewed to the right as indicated in FIG. 10. For many sizes, especially for sizes smaller than 200 or greater than 2000 DNA base-pairs, there is only one gene in a given size and the observation of transposon insertions for small genes are usually truncated. Since all genes are modeled simultaneously in a single model with a prior γ enforcing the essentialness of a gene being independent of its size, the sparseness of the data does not impose limitations on the computation. However, as discussed in the next section, the prior may play a dominating role for small genes where data are sparse. The estimations of γ and λ, together with the 95 percent BCa confidence intervals are presented in Table 6 and the estimation of {right arrow over (N)} is presented in FIG. 16.







TABLE 6







Parameter Estimation of γ and λ















BCa Confidence



Estimate
Bias
SE
Intervals















γ
0.8434
 3.942 × 10−3
9.893 × 10−3
(0.818, 0.859)


λ
2.547 × 10−3
−1.027 × 10−5
4.392 × 10−5
(0.00247, 0.00264)





Here the bias and standard error are estimated with bootstrap






    2. Multivariate Model with Grouped Gene Sizes


The prior γ plays an important role in enforcing the fact that the essentialness of a gene is independent of its size. It also made possible to estimate the number of essential genes where data are very sparse. However, for small genes where data are extremely sparse, the prior γ becomes the dominating source of information. In order to moderate the dominance of the prior on small genes with sparse observations, we grouped the genes into 143 groups according to their sizes, using the median size of each group as the gene size. Table 7 is a sample of estimated {right arrow over (N)} based on grouped and exact gene sizes. In the table, m is the number of unique sizes in each group; N1 is estimated using grouped data and N2 is estimated using ungrouped data.







TABLE 7







Estimated N with Grouped and Exact Gene Sizes













Gene size
m
M
x
N
N1
N2
















 [72, 120]
6
7
3
2
6
7


(120, 150]
4
7
3
2
6
7


(150, 160]
3
7
2
2
6
7


(160, 170]
2
8
0
0
7
7


(170, 180]
3
9
1
1
8
8


(180, 190]
3
9
1
1
8
8


(190, 200]
3
12
4
4
11
11


(200, 210]
4
27
7
7
23
24


(210, 220]
3
19
7
5
16
17


. . .
. . .
. . .
. . .
. . .
. . .
. . .









We see that here N2≧N1, However, this is true only for data in the above table where the ungrouped data are extremely sparse and most of the data are truncated. The estimated proportion of non-essential genes, γ, is actually larger for grouped data which is presented in Table 8. Grouping genes with similar sizes reduces the sparseness of the data and consequently, the dominance of the prior. Another obvious advantage of grouping is dimension reduction of the parameter space, and therefore, drastic reduction of computation time. Of cause, such grouping introduces another source of variation, and the algorithm could be unrobust against different grouping. In our study, however, different grouping resulted only in slight difference in estimates.

    3. Conditional Maximum Likelihood Estimates


For a given gene size δj, the likelihood function (3.4) can be written differently as




  
    
      
        
          
            L
            j
          
          ⁡
          
            (
            
              γ
              ,
              
                λ
                |
                
                  N
                  j
                
              
            
            )
          
        
        =
        
          
            (
            
              
                
                  
                    N
                    j
                  
                
              
              
                
                  
                    n
                    j
                  
                
              
            
            )
          
          ⁢
          
            q
            j
            
              n
              j
            
          
          ⁢
          
            p
            j
            
              
                N
                j
              
              -
              
                n
                j
              
            
          
          ⁢
          
            
              ∏
              
                i
                =
                1
              
              
                n
                j
              
            
            ⁢
            
              f
              ⁡
              
                (
                
                  
                    x
                    
                      j
                      ,
                      i
                    
                    *
                  
                  ,
                  
                    
                      δ
                      j
                    
                    ⁢
                    λ
                  
                
                )
              
            
          
        
      
    
    
      
        (
        5.1
        )
      
    
  




Here ƒ(. , .) is defined in (3.1), and xj,1*,xj,2*, . . . ,xj,nj* are the nj nonzero observations from Nj genes of size δj. Assume there are g different gene sizes, the likelihood function can be written as




  
    
      
        
          L
          =
          
            
              
                (
                
                  
                    ∏
                    
                      j
                      =
                      1
                    
                    g
                  
                  ⁢
                  
                    
                      (
                      
                        
                          
                            
                              N
                              j
                            
                          
                        
                        
                          
                            
                              n
                              j
                            
                          
                        
                      
                      )
                    
                    ⁢
                    
                      q
                      j
                      
                        n
                        j
                      
                    
                    ⁢
                    
                      p
                      j
                      
                        
                          N
                          j
                        
                        -
                        
                          n
                          j
                        
                      
                    
                  
                
                )
              
              ·
              
                (
                
                  
                    ∏
                    
                      j
                      =
                      1
                    
                    g
                  
                  ⁢
                  
                    
                      ∏
                      
                        i
                        =
                        1
                      
                      
                        n
                        j
                      
                    
                    ⁢
                    
                      f
                      ⁡
                      
                        (
                        
                          
                            x
                            
                              j
                              ,
                              i
                            
                            *
                          
                          ,
                          
                            
                              δ
                              j
                            
                            ⁢
                            λ
                          
                        
                        )
                      
                    
                  
                
                )
              
            
            =
            
              
                L
                1
              
              ·
              
                L
                2
              
            
          
        
        ⁢
        
          

        
        ⁢
        with
        ⁢
        
          

        
        ⁢
        
          
            
              ∑
              
                j
                =
                1
              
              g
            
            ⁢
            
              n
              j
            
          
          =
          
            n
            .
          
        
      
    
    
      
        (
        5.2
        )
      
    
  




Assuming the number of observations nj for each gene size δj being fixed, we can obtain the conditional maximum likelihood estimate of λ by maximize L2 as




  
    
      
        
          
            
              λ
              ^
            
            =
            
              
                
                S
                
              
              /
              
                
                  ∑
                  
                    j
                    =
                    1
                  
                  g
                
                ⁢
                
                  
                    n
                    j
                  
                  ⁢
                  
                    
                      δ
                      j
                    
                    
                      1
                      -
                      
                        e
                        
                          
                            -
                            
                              λ
                              ^
                            
                          
                          ⁢
                          
                            δ
                            j
                          
                        
                      
                    
                  
                
              
            
          
          ,
          
            

          
          ⁢
          where
        
        ⁢
        
          

        
        ⁢
        
          
            
            S
            
          
          =
          
            
              
                ∑
                
                  j
                  =
                  1
                
                g
              
              ⁢
              
                
                  ∑
                  
                    i
                    =
                    1
                  
                  
                    n
                    j
                  
                
                ⁢
                
                  x
                  
                    j
                    ,
                    i
                  
                  *
                
              
            
            =
            
              
                ∑
                
                  i
                  =
                  1
                
                n
              
              ⁢
              
                
                  x
                  i
                  *
                
                .
              
            
          
        
      
    
    
      
        (
        5.3
        )
      
    
  




Equation (5.3) reduces to equation (4.2) if we estimate Nj by




  
    N
    j
  
  =
  
    
      
        n
        j
      
      
        1
        -
        
          e
          
            
              -
              
                λ
                ^
              
            
            ⁢
            
              δ
              j
            
          
        
      
    
    .
  




The proportion of truncated nonessential genes can be calculated as




  
    
      
        
          p
          ^
        
        =
        
          
            P
            ⁡
            
              (
              
                x
                =
                
                  0
                  ⁢
                  
                    ❘
                  
                  ⁢
                  non
                  ⁢
                  
                    
                  
                  ⁢
                  essential
                
              
              )
            
          
          =
          
            
              ∫
              Ω
            
            ⁢
            
              
                e
                
                  
                    -
                    
                      λ
                      ^
                    
                  
                  ⁢
                  
                    
                  
                  ⁢
                  δ
                
              
              ⁢
              
                
                  d
                  
                    F
                    ⁡
                    
                      (
                      δ
                      )
                    
                  
                
                .
              
            
          
        
      
    
    
      
        (
        5.4
        )
      
    
  




Here Ω is the set of nonessential genes, which can be approximated by the set of all untruncated genes.
Therefore,




  
    
      
        
          γ
          ^
        
        =
        
          
            n
            M
          
          +
          
            p
            ^
          
        
      
    
    
      
        (
        5.5
        )
      
    
  




Estimations from the three approaches are very similar as shown in Table 8. If the primary interest is to estimate λ and γ, the conditional MLE approach has the advantage of simplicity. However, in estimating λ, this approach omitted information of {right arrow over (M)}, and γ is estimated separately after λ is estimated. Another obvious limitation of this approach is that it can only estimate ∥{right arrow over (N)}∥, the total number of nonessential genes by ∥{right arrow over (n)}∥/{circumflex over (γ)}. The estimation of {right arrow over (N)} by {right arrow over (n)}/{circumflex over (γ)} is not reasonable because even though γ is independent of gene size, we can not assume the proportion of non-essential genes in different sizes being the same as shown in FIG. 17.








TABLE 8







Estimates of γ and λ, with the Three Approaches















95% BCa



Estimates
Bias
SE
Confidence intervals
















Multivariate Model with
γ
0.843
3.942 × 10−3
9.893 × 10−3
(0.818, 0.859)


Exact Gene Sizes
λ
2.547 × 10−3
−1.024 × 10−5 
4.320 × 10−5
(2.473, 2.642) × 10−3


Multivariate Model with
γ
0.853
7.221 × 10−4
8.051 × 10−3
(0.835, 0.867)


Grouped Gene Sizes
λ
2.524 × 10−3
2.803 × 10−6
4.063 × 10−5
(2.451, 2.610) × 10−3


Conditional Maximum
γ
0.828
−7.621 × 10−5 
7.273 × 10−3
(0.815, 0.843)


Likelihood Estimates
λ
2.539 × 10−3
9.713 × 10−7
4.058 × 10−5
(2.455, 2.618) × 10−3









E. Discussion of One Dimentsional Case

When the model does not depend on gene size, which can happen for example, when we study a subset of genes with a fixed size, or in other settings where the distribution is identical, model (2.6) reduces to (2.5). Blumenthal, Dayhiya, and Gross (1978) studies estimations of complete sample size from an incomplete Poisson sample using conditional, unconditional, and modified maximum likelihood functions. The modified likelihood estimation weights the likelihood function and maximizes it. This approach is similar to providing priors to λ and N. Table 9 presents four types of estimations of N using data randomly selected from the 143 grouped genes. Here M and n are number of genes and number of genes with at least one observed transposon insertions. Nm-b is a subset of N1 in Table 7, which is estimated using model (2.6) with grouped data; Nb is estimated with model (2.5); Nc and Nu are conditional and unconditional estimates of N as described in Blumenthal., Dayhiya, and Gross (1978).







TABLE 9







Comparison of Estimations with Different Methods













Gene size
M
n
Nm−b
Nb
Nu
Nc
















[72, 120]
7
2
6
2
3
2


(400–410]
44
31
40
37
36
36


(430–440]
46
22
38
25
25
26


(470–480]
80
42
66
57
56
57


(500–510]
54
30
45
39
39
39


(610–620]
47
29
39
33
33
34


(640–650]
54
35
45
44
43
43


(710–720]
50
35
42
41
41
41


(750–760]
56
37
46
39
46
40


(770–780]
61
43
51
53
52
52


(910–920]
60
47
52
53
53
52


(980–990]
57
45
49
52
51
51


(1050–1100]
137
107
115
117
115
117


(1200–1250]
129
100
106
106
106
106


(1400–1450]
121
110
111
112
112
112


(2100–2150]
23
20
20
20
20
20









We see that the estimations from the three univariate models are very similar. For fairly large genes, estimations from the multivariate model are similar to those of the univariate models. However, for small genes with high truncation rate, estimations from the multivariate model are larger than estimations from the univariate models. In the univariate models, only the information related to a particular gene size is used and the estimations are obtained separately for each gene size. This approach tends to underestimate N for small genes with sparse observations. The multivariate model uses a prior to enforce the fact that the essentialness of a gene is independent of its size and maximizes the likelihood jointly for all genes. Therefore, it alleviates the underestimation of N for small genes with high truncation rate.
Example 2
lpxC
Lipid A constitutes the outer layer of the outer membranes of gram-negative bacteria and is essential for bacterial growth. This makes all the enzymes involved in the biosynthesis of this molecule essential for bacterial growth, and therefore ideal targets for drug design. A series of synthetic molecules was previously identified that inhibited the first committed step in lipid A biosynthesis. Onishi H. R., B. A. Pelak, L. S. Gerckens, L. L. Silver, F. M Kahan, M-H Chen, A. A. Patchett, S. M. Galloway, S. A. Hyland, M. S. Anderson, and C. R. H. Raetz. 1996. Science. 274: 980-982. This step is catalyzed by a unique deacetylase (UDP-3-O-[R-3-hydroxymyristoyl]-GlcNAc deacetylase), LpxC.
UDP-3-O-[R-3-hydroxymyristoyl]-GlcNAc deacetylase (LpxC) is a deacetylase that catalyzes the first committed step of lipopolysaccharide (LPS) biosynthesis in gram negative bacteria. This is the second step following the first acylation of N-Acetylglucosamine (GlcNAc). This enzyme functions to deacetylate the UDP-3-O-[R-3-hydroxymyristoyl]-GlcNAc. This step was shown to be essential for growth in E. coli wherein a point mutant (EnvA1) expresses an LpxC protein that has reduced activity. Beall B. and J. Lutkenhaus, 1987. Sequence analysis, transcriptional organization, and insertional mutagenesis of the envA gene of Escherichia coli. J. Bacteriol. 169: 5408-5415. A 30% reduction in the amount of LPS on the cell wall of such mutants results in hypersensitivity to antibiotics. Attempts to create null mutants in lpxC were unsuccessful in a number of pathogenic bacteria, indicating that inhibitors of LpxC would be effective antibiotics for a number of gram negative organisms.
Previously identified inhibitors are chiral hydroxamic acids that had unique hydrophobic aromatic moieties, and were suspected to bind a metal in the active site of the deacetylase. The most potent inhibitor, L-161,240, displayed a minimal inhibitory concentration of about 1 microgram per milliliter against E. coli, caused three logs of bacterial killing in 4 hours, and cured mice infected with a lethal intraperitoneal dose of E. coli. Considering the very high degree of homology between the E. coli and P. aeruginosa enzymes, it was initially presumed that an inhibitor of the E. coli enzyme might also inhibit the P. aeruginosa enzyme. However, this molecule inhibited LpxC from P. aeruginosa only at very high concentrations, and even then it did so poorly. It had no effect on bacterial growth in this organism. Thus, there was some question as to whether the lpxC homologue had the same function in P. aeruginosa, and whether it was essential to P. aeruginosa given its decreased sensitivity to the L,161,240 inhibitor.
Nevertheless, P. aeruginosa lpxC was one nucleic acid identified as being unable to accommodate a transposon insertion in the library depicted in Table 1 (PA4406). To test the essentiality of P. aeruginosa lpxC, we first tested the sensitivity of P. aeruginosa transformants expressing E. coli LpxC following a “promoter swap” integration. Using this technique, we completely shut off expression of the native P. aeruginosa lpxC, while expressing only the E. coli enzyme encoded on a plasmid. This strategy resulted in a P. aeruginosa mutant that was more sensitive to L-161,240. This suggested that the E coli lpxC gene was substituting for the function of the P. aeruginosa gene, and moreover, that there were no duplicate functional homologues in P. aeruginosa that were active in the absence of lpxC.
Materials. Pseudomonas aeruginosa PAO1 was grown at 37° C. in Luria-Bertani (LB) broth (Difco) or plated on sheep blood agar (Remel). Tetracycline at 100 μg/ml in LB media was used to maintain the selection of the integrated plasmid pBEM10 in PAO1. LB broth or agarwith 10 μg/ml of tetracycline was used for growing E. coli DH5α (Gibco BRL) and E. coli S-17 transformants. Plasmids pPS72 and pBADHisB were from Promega and Invitrogen, respectively. EDTA, bis-tri buffer, sucrose, arabinose, and DMSO were purchased from Sigma as Ultrapure agents. Yeast extract and Tryptone were obtained from Difco. Restriction enzymes, and T4 DNA Ligase, and their reaction buffers were from New England Biolabs. Polymixin B nonapeptide was from Sigma. The antibiotics, tetracycline, ampicillin, carbenicillin, gentamicin, and kanamycin were all purchased from Sigma. DNA and deduced amino acid information were analyzed using a family of programs included in the Dnastar package. BLASTP was used to search for amino acid similarities among a host of protein databases available on-line through the National Library of Medicine (USA). Altschul, T. F., W. Gish, W. Miller, E. W. Myers, and D. J. Lipman. 1990. Basic local alignment tool. J. Mol. Biol. 215: 403-410.
DNA manipulations. Standard recombinant DNA procedures were used. Sambrook J., E. F. Fritsch, and T. Maniatis. 1989. Molecular cloning: a Laboratory Manual, 2nd Edition. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory. Primers were designed to the N- and C-terminal regions of the E. coli or P. aeruginosa lpxC gene that encompassed only the coding region and included NdeI and EcoRI restriction sites for subsequent cloning. For the E. coli gene the primers were (5′-GGGAATTCCATATGATCAAACAAAGGACACTTAAACGT-3′ and 5′-CCGGAATTCTTATGCCAGTACAGCTGAAGGCGCT-3′) (SEQ ID NOS:1 and 2) and for the P. aeruginosa gene they were (5′-GGGAATTCCATATGATGATCAAACAACGCACCTTGAAGAACAT-3′ and 5′-CCGGAATTCCTACACTGCCGCCGCCGGGCGCATATAG-3′) (SEQ ID NOS:3 and 4). These primers were used in a polymerase chain reaction (PCR) containing either P. aeruginosa genomic DNA (10-50 μg) or plasmid pKD6 containing the E. coli lpxC gene (1.0 μg) as template (Sorensen, P. G., J. Lutkenhaus, K. Young, S. S. Eveland, M. S. Anderson, and c.R.H. Raetz. 1996. Regulation of UDP-3-O-[R-hydroxymyristoyl]-N-acetylglucosamine deacetylase in Escherichia coli. The second enzymatic step of lipid A bioynthesis. J. Biol. Chem. 271 (42): 25898-25905). The lpxC genes were amplified using Pwo DNA polymerase (Roche) in a 100 μl reaction mixture containing 200 μM concentration of each dNTP and 0.5 μM concentration of each primer for 30 cycles (94° C. denaturation, 55° C. annealing, and 72° C. polymerization (according to the manufacturer's instructions). The PCR products were purified with the Qiaquick PCR Purification Kit from Qiagen (according to the manufacturer's instructions) and digested with NdeI and EcoRI restriction enzymes at sites introduced by the primer sequences. Bands of the correct sizes predicted for the lpxC genes were separated by gel electrophoresis, and the excised DNA purified using the Qiaquick Gel Extraction Kit from Qiagen (according to the manufacturer's instructions). The purified DNA was ligated into the T7 expression vector (Studier, F. W., A. H. Rosenberg, J. J. Dunn, and J. W. Dubendorff. 1990. Use of T7 RNA polymerase to direct expression of cloned genes. Methods Enzymol. 185: 60-89). Plasmid pET21b (Novagen), that had been cut in the multiple cloning site with the same enzymes, was transformed into DH5α and plated on LB agar containing ampicillin (250 μg/ml). The resulting clones had their DNA sequenced to confirm the fidelity of the PCR reactions before it could be transferred into the expression strain. Subcloning of these fragments into other vectors was carried out as needed for expression in various backgrounds. These included pEX18T (cbR) for allelic exchange mutagenesis in P. aeruginosa (Schweizer, H. P. and T. T. Hoang. 1995. An improved system for gene replacement and xylE fusion analysis in Pseudomonas aeruginosa. Gene 158(1): 15-22), pDN19 (tetR) for low copy number complementation of E. coli JBK-1 (Nunn, D., S. Bergman, and S. Lory. 1990. Products of three accessory genes, pilB, pilC, and pilD, are required for biogenesis of Pseudomonas aeruginosa pili. J. Bacteriol. 172(6): 2911-2919), and pUCP30T (gmR) for P. aeruginosa ‘promoter swap’ mutant complementation (Schweizer, H. P., T. R. Classen, and T. Hoang. 1996. Improved methods for gene analysis and expression in Pseudomonas. In: Nakazawa, T., K. Furukawa, D. Haas, S. Silver. (Eds.) Molecular Biology of Pseudomonas. American Society for Microbiology, Washington, D.C. pp. 229-237).
Construction of pBEM10 and ‘promoter swap’ mutagenesis. Plasmid pPW101 was made by ligating oriT, the region that encodes conjugative plasmid transfer, into pSP72 (Promega). oriT had been amplified from plasmid pEX100T (Schweizer and Hoang, 1995, supra) with an introduction of an NdeI and AatII restriction sites. To create the lpxC ‘promoter swap’ vector, pBEM10, the following different DNA pieces were amplified and sequentially ligated into pPW101. These included the tetracycline resistance marker (tetR) from plasmid pUCP26 (Olsen, R. H., G. DeBusscher and R. R. McCombie. 1982. Development of broad-host-range vectors and gene banks: self-cloning of the Pseudomonas aeruginosa PAO chromosome. J. Bacteriol. 150: 60-69), the araBAD promoter from the plasmid pBAD HisB (Invitrogen) with an altered ribosome binding site (rbs) (Guzman, L. M., D. Belin, M. J. Carson, and J. Beckwith. 1995. Tight regulation, modulation, and high-level expression by vectors containing the arabinose pBAD promoter. J. Bacteriol. 177(14):4121-4130), the araC gene, also from pBAD HisB (Lee, N. 1980. Molecular aspects of ara regulation. In The Operon. J. H. Miller and W. S. Reznikoff, eds. Cold Spring Harbor, N.Y. Cold Spring Harbor Laboratory, pp. 389-410; and Schleif, R. S. 1992. DNA looping. Ann. Rev. Biochem. 61: 199-223), and the first 340 base pairs of the P. aeruginosa lpxC gene. The tetR marker was amplified using a forward primer that introduced a BglII site (5′-AGATCTCAAGGGTTGGTTTGCGCA-3′, SEQ ID NO:5) and a reverse primer that introduced an EcoRI site (5′-GAATTCTAATTCTCATGTTTGACA-3′, SEQ ID NO:6). The araBAD promoter and araC gene were amplified as one piece from the pBAD HisB vector. The forward primer introduced an XhoI site (5′-CTCGAGGCATGCATAATGTGCCTGTC-3′, SEQ ID NO:7) and the reverse primer introduced a HindIII site (5′-AAGCTTCTCCTGTTAGCCCAAAAAAACG-3′, SEQ ID NO:8). The rbs was altered from its original AGGAG to CTTCT. The following primer set was used to make these changes and introduced an upstream BssHII site (5′-GCGCGCGGACGAAAGTAAACCCACTGG-3′, SEQ ID NO:9) and a downstream HindIII site (5′-AAGCTTATTCAGAAGGTTAGCCCAAAAAAACGGG-3′, SEQ ID NO:10). The first 340 bases of PAO1 lpxC were amplified from PAO1 genomic DNA. The forward primer introduced a HindIII site (5′AAGCTTATGATCAAACAACGCACCTT-3′, SEQ ID NO:11) and the reverse primer introduced an XbaI site (5′-TCTAGAAGCGCTGCCATCCATGATCGG-3′, SEQ ID NO:12). These pieces were then ligated into pPW101 to form the final product, pBEM10, which was used for the ‘promoter swap’ mutagenesis of lpxC. The ‘promoter swap’ scheme is a homologous recombination strategy, whereby transformation of pBEM10 into P. aeruginosa removed the native lpxC promoter and placed the tightly regulated araBAD promoter upstream of the chromosomal copy of lpxC, allowing modulation of its expression by the use of a simple sugar, arabinose (FIG. 3). In the absence of arabinose the lpxC was effectively shut off, and expression was inducible by addition of arabinose. Such mutants were selected in the presence of arabinose, and if lpxC is essential, these mutants would not be viable in media that is not supplemented with arabinose, but fully capable of growth in the presence of arabinose.
Growth curves. Bacterial cultures were prepared by diluting stationary phase overnight cultures to an OD600 of 0.1 in 5 ml of LB. The inhibitor, L-161,240, was resuspended in DMSO to a final concentration of 10 mg/ml and added to the bacterial cultures to a final concentration of 50 μg/ml or 10 μg/ml. In the samples without inhibitor, DMSO was added to keep the final concentration of DMSO equivalent between samples. The cultures were incubated with shaking and 0.8 ml was taken for OD600 readings over the course of the experiment. DH5α, PA01, and PA0200 (Schweizer, H. P. 1998. Intrinsic resistance to inhibitors of fatty acid biosynthesis in Pseudomonas aeruginosa is due to efflux: application of a novel technique for generation of unmarked chromosomal mutations for the study of efflux systems. Antimicrob. Agents Chemother. 42: 394-398) were all grown at 37° C. In the cases where temperature sensitive JBK strains were being assayed, the cultures were grown at 42° C. for both the overnight and the time course cultures.
Outer membrane permeabilization. Polymixin B nonapeptide (Sigma) was prepared as a suspension in DMSO at 3 mg/ml final concentration. Erythromycin and Tetracycline were resuspended in DMSO to a final concentration of 250 mg/ml and 125 mg/ml, respectively. L-161,240 was prepared as above in DMSO to a final concentration of 10 mg/ml. These DMSO antibiotic solutions were individually added to LB to the appropriate final concentration and mixed. Polymixin B nonapeptide was then added to the appropriate samples and mixed. DMSO was added to each sample to keep the final concentration of DMSO equivalent between samples. A stationary phase overnight culture of PA01 was added to each sample to bring the final concentration to 0.1 OD600. Samples were removed for OD600 determinations every 1-2 hours for 6.5 hours and the data from these time points were plotted.
MIC determinations for ‘promoter swapped’ mutants. Single colonies of DH5α, PA01 and each promoter swap strain were picked and grown in LB at 37° C. with shaking for approximately 4 hours. Assuming that an OD600 reading of 1.0 is equivalent to 109 cells/ml, dilutions were made of all cultures to 5×105 cells/ml. 200 μl of each diluted culture was added to each well where a two-fold serial dilution of inhibitor had been placed. The 96-well plates were incubated at 37° C. overnight and their OD600 determined using the Spectramax Plus (Molecular Devices) plate reader.
To confirm the effect of the arabinose-sensitive promoter in regulating the lpxC expression in the swapped mutants, MIC determinations were performed as above, except that arabinose was added to induce expression of the chromosomal locus and override the effects of the plasmid borne lpxC. In this case the stationary-phase overnight bacterial culture was diluted to 5×105 cells/ml in LB containing Arabinose to a final concentration of 0.2% (a 20% stock made up in water).
RESULTS AND DISCUSSION
Homology between the E. coli and the P. aeruginosa LpxC enzymes. Using protein analysis software, this study and others have compared the deduced amino acid sequence of LpxC from both E. coli and P. aeruginosa (Hyland, S. A., S. S. Eveland, and M. S. Anderson. 1997. Cloning, expression, and Purification of UDP-3-O-Acyl-GlcNAc Deacetylase from Pseudomonas aeruginosa: a metalloamidase of the lipid A biosynthesis pathway. J. Bacteriol. 179 (6): 2029-2037). This comparison revealed 82% similarity and 57% identity shared between the two sequences. This homology was found over the entire length of the protein sequence (data not shown). Significant homology with other known acetyl- or acyltransferases was not found, suggesting that LpxC is unique among acetyltranferases. The two proteins also share a total of five fully conserved Histidine residues that are presumed to be responsible for the zinc metal cofactor coordination. It was therefore expected that an inhibitor that functions by chelating the metal cofactor away would affect both enzymes similarly.
LpxC is essential for growth in P. aeruginosa. Since the hydroxamate inhibitor was effective in preventing growth of E. coli, but completely ineffective against P. aeruginosa, there was a possibility that LpxC was not essential in P. aeruginosa. This could be as a result of the presence of another enzyme that catalyzed a similar function. If that were the case, elimination of the LpxC function should be possible without inhibiting bacterial growth. A thorough analysis of the P. aeruginosa genome sequence revealed only one LpxC homologue. An attempt to disrupt the function of this LpxC homologue was made by conjugating wild type PAO1 with a suicide vector (pEX18T) carrying lpxC whose BamHI-SalI fragment had been replaced with a gentamicin cassette. However, P. aeruginosa null mutants could not be established by this method. In several attempts a few gentamicin resistant trans-conjugants were obtained, but in all these cases allelic replacement of the chromosomal lpxC by the defective copy had not occurred. Instead, a gene duplication had occurred, placing the suicide vector and the disrupted copy next to the wild type allele (data not shown). This could be demonstrated by the carbenicillin resistance and sucrose sensitivity acquired by these trans-conjugants, both of which are encoded on the suicide vector. These data indicated a strong negative selection for the sought after disruption of lpxC suggesting that lpxC is essential for growth. To confirm this, an experiment was carried out whereby the trans-conjugants were transformed with either lpxC on a low copy, replicating vector, or vector alone. In 100% of lpxC transformants, resolution of the gene duplication as demonstrated by the loss of carbenicillin resistance and sucrose sensitivity was observed, as opposed to no such resolution among those transformed with vector alone. These results suggested that the wild type genomic allele could be disrupted if a functional copy was present on the transforming plasmid.
In another attempt at demonstrating essentiality of LpxC in P. aeruginosa, the ‘promoter swap’ strategy as described in materials and methods was carried out. ‘Promoter swapped’ pseudomonas mutants were fully capable of growth in the presence of arabinose when the arabinose sensitive lpxC promoter was turned on, but completely incapable of growth in the absence of this inducer. This further confirmed that in P. aeruginosa, just as in E. coli, LpxC is essential for growth.
E. coil expressing LpxC from P. aeruginosa is more resistant to L-161, 240. The E. coli strain JBK-1/pKD6 contains the chromosomal lpxC gene disrupted with a kan element and a wild type copy of E. coli lpxC on the temperature-sensitive replicon pKD6. The strain was constructed as described by Sorensen et al., 1996. Since lpxC is essential for growth, this strain is not viable at 42° C. because the functional copy is on the temperature sensitive replicon. Transforming JBK-1/pKD6 with lpxC from either E. coli or P. aeruginosa on a non-temperature-sensitive replicon (pKD19, TetR) and selecting at 42° C., produced transformants that were viable at 42° C., tetracycline resistant, and kanamycin sensitive. This result indicated that lpxC from P. aeruginosa could be expressed in the E. coli background, and was capable of substituting for the missing chromosomal copy. An unexpected result was that whereas the JBK-1 carrying the lpxC copy from E. coli was still sensitive to killing by a slightly higher concentration of L-161,240, the JBK-1 carrying the lpxC copy from P. aeruginosa was resistant to up to 50 μg/ml, about 50 times above the MIC of the wild type organisms (data not shown). This suggested that the P. aeruginosa enzyme was uniquely resistant to this inhibitor. It also meant that this resistance was the reason for the failure to inhibit growth of P. aeruginosa, and not reduced permeability, or efflux or modification of drug by the pseudomonal enzymes. This, in turn, suggests that a program designed to search for inhibitors for the pseudomonal enzyme should be based on screening directly on that enzyme, and not the surrogate enzyme from E. coli. 
L-161, 240 is a substrate for the major drug efflux pump of P. aeruginosa. The completed P. aeruginosa genome reveals genes for at least nine homologous, multicomponent, multidrug efflux systems (Stover et al., 2000, Complete genome sequence of Pseudomonas aeruginosa PA01, an opportunistic pathogen, Nature 406: 959-64). However the only one that is constitutively expressed to a high degree in the wild type strains is MexAB-OprM (Kohler, T., M. Michea-Hamzehpour, and U. Henze. 1997. Characterization of MexE-MexF-OprN, a positively regulated multidrug efflux system of Pseudomonas aeruginosa. Mol. Microbiol. 23: 345-354). Therefore, mutants of this efflux system can be used to evaluate the consequences of diminished efflux pump activity. These mutants would be expected to be highly sensitive to a number of antibiotics. Such a mutant, PAO 200, has been isolated (Schweizer, 1998, supra), and whereas it shows a higher level of sensitivity to a number of antibiotics (Westbrock-Wadman, S. D. R. Sherman, M. J. Hickey, S. N. Coulter, Y. Q. Zhu, P. Warrener, L. Y. Nguyen, R. M. Shawar, K. R. Folger, and C. K Stover. 1999. Characterization of a Pseudomonas aeruginosa Efflux Pump Contributing to Aminoglycoside Impermeability. Antimicrobial Agents and Chemotherapy. 43 (12): 2975-2983), it was not more sensitive to L-161,240 (FIG. 4). This suggests that this drug compound is not a substrate for this efflux system in P. aeruginosa. 
P. aeruginosa is not less permeable to L-161,240. Low permeability of the outer membrane is a major contributing factor to the observed high levels of intrinsic drug resistance in P. aeruginosa (Nikaido, H. 1998. The role of outer membrane and efflux pumps in the resistance of gram-negative bacteria. Can we improve access? Drug Resistance Updates. 1: 93-98). This low permeability is due to the fact that P. aeruginosa lacks the homolog of the relatively efficient, trimeric porins like OmpF. P. aeruginosa has, instead, OprF, the OmpA homolog, which produces channels only when it is folded into a rare conformation, and only a small fraction of these channels occurs in the open conformation. As is usually the case with P. aeruginosa it was assumed that the reason L-161,240 was ineffective against P. aeruginosa was the lack of permeability of the outer membrane to this inhibitor. Polymixin B nonapeptide (PMBN), a derivative of Polymixin B that lacks the fatty acid tail, is capable of binding to the polyanionic LPS molecules and disrupting the bilayer structure, thus increasing the permeability of the outer membrane. PMBN has been used this way to permeabilize the outer membrane of many gram-negative bacteria (Vaara, M. and T. Vaara. 1983. Sensitization of gram-negative bacteria to antibiotics and complement by a nontoxic oligopeptide. Nature 303: 526-528), including P. aeruginosa (Vilianen, P. and M. Vaara, 1984. Susceptibility of gram-negative bacteria to polymixin B nonapeptide. Antimicro Agents Chemother. 25: 701-705) and effectively sensitize them to lipophilic antibiotics. Unlike the acylated polymixin B, PMBN is not cidal. In order to determine the effect of outer membrane exclusion of L-161,240, we exposed P. aeruginosa to PMBN in combination with L-161,240, and with other lipophilic antibiotics as positive controls. Whereas PMBN lowered the MIC of tetracycline for P. aeruginosa more than 16 fold, the sensitivity towards L-161,240 remained unchanged (FIG. 5). This, together with the E. coli expression data indicated that permeability was not a major factor causing the inability of L-161,240 to inhibit pseudomonal growth.
P. aeruginosa expressing only E. coli LpxC is more sensitive to L161-240 than wild type. Using the ‘promoter swap’ technique as described in the methods, it was possible to replace expression from the wild type chromosomal copy of P. aeruginosa lpxC, with expression solely from a plasmid borne copy. For this experiment, ‘promoter swapped’ P. aeruginosa was transformed with either vector containing P. aeruginosa lpxC (“PA Swap #1”), or vector containing E. coli lpxC (“PA Swap #2’). The transformants were then exposed to various concentrations of L-161,240 for MIC determination. Transformants expressing the E. coli enzyme only were much more sensitive to the inhibitor compared to organisms expressing the P. aeruginosa enzyme (FIG. 6). These transformants were sensitive enough to b comparable with the sensitivity seen in E. coli. Since the validity of this observation relied on the un-induced arabinose-sensitive promoter to shut down expression from the chromosomal copy of lpxC, it was necessary to demonstrate how effectively this happens. To do that, MIC determinations were performed as above, except that arabinose was added to induce expression of the chromosomal locus. For this experiment stationary-phase overnight bacterial cultures were diluted to 5×105 cells/ml in LB containing 0.2% arabinose. In this case all the transformants, regardless of what gene the vector contained, were resistant to killing due to the expression of the chromosomal copy of P. aeruginosa lpxC. This confirmed that certain intrinsic properties of the P. aeruginosa enzyme are resistant to inhibition by this hydroxamate inhibitor. It also confirmed that neither reduced uptake, efflux, nor modification of the inhibitor play a significant role in this observed resistance. Considering the very high similarity between the two enzymes, this finding was not expected.
But on further examination and analysis of existing data, it was possible to recognize some inherent differences that might explain this finding. Whereas both these enzymes share five conserved Histidine residues, the E. coli enzyme has two more Histidines that have no counterparts in the P. aeruginosa enzyme. This is an important difference because these residues are probably involved in the metal cofactor coordination. It was also observed earlier that whereas the E. coli enzyme is not sensitive to EDTA, the P. aeruginosa enzyme was significantly inhibited by as little as 2 μM EDTA. Evidence that the E. coli enzyme is also a metalloenzyme is that the envA1 mutation, which has one of the conserved Histidines (His 19) replaced by a Serine, is sensitive to EDTA. It was because of these observations that these investigators suggested that the E. coli enzyme has a more stably bound metal than that of the EnvA1 mutant protein, and thus it is less accessible to EDTA than the wild type P. aeruginosa enzyme. These observations suggest that the Histidine ‘patch’ that is involved in the metal coordination is not similar between the two enzymes. It is conceivable therefore that since the inhibitor works by chelating the metal cofactor away from the enzyme, each ‘patch’ has unique features that result in disparate reactivities towards the inhibitor. It is also important to consider the findings of Wyckoff et al., 1998. Hydrocarbon rulers in UDP-N-acetylglucosamine acyltransferases. J. Biol. Chem. 273 (49): 32369-32372. These investigators found that LpxA, the first enzyme of lipid A biosynthesis, is very selective for the length of its acyl donor substrates. Whereas E. coli LpxA prefers R-3-hydroxymyristoyl-ACP to R-3-hydroxydecanoyl-ACP, P. aeruginosa LpxA prefers the opposite. The products of the LpxA reaction therefore differ in the carbon chain length of their lipid moieties between the two bacteria. Since the product of the LpxA reaction is the substrate of the LpxC reaction, this observation suggests that the two LpxCs would have substrate binding pockets of different sizes to accommodate the different size substrate. That would, in turn, suggest that inhibitors that have to occupy that active site would be unique for each enzyme.
Examples 3-7
ispA, ispB, uppS, aroC, aroK and metK
Several more candidate genes from the HTTIM gene database were tested for essentiality using a single crossover knock-out strategy. The Pseudomonas genes targeted for knocking out were ispA, ispB, uppS, metK, aroC, and aroK. To attempt knock-outs, regions of about 300 bp were cloned into the vector pPW120. These regions were selected so that known active site residues (or highly conserved residues likely to be essential for enzyme function) would be separated after generation of a single-crossover knock-out. The regions were (numbering from the start codon): ispA, 283-594; ispB, 319-610; uppS, 103-402; metK, 415-732; aroC, 385-684; aroK, 175-375.
The pPW120 vector carries an E. coli origin of replication, but not a Pseudomonas origin of replication, making it a suicide vector. It also carries an origin of conjugal transfer and antibiotic resistance genes for tetracycline and ampicillin. An E. coli donor strain (SM10) carrying the pPW120 knockout constructs was incubated with Pseudomonas strain PAO1 to allow conjugal transfer, and recombinants were selected by plating onto media containing tetracycline at 100 μg/mL and chloramphenicol at 10 μg/mL. Pseudomonas recombinants will be resistant to this antibiotic mixture while wild-type PAO1 and the E. coli donor strain will be sensitive. Aromatic amino acid recombinants (aroC and aroK) were then tested for auxotrophy by plating onto minimal media with and without phenylalanine, tryptophan, tyrosine, and folic acid at 100 μg/mL while maintaining tetracycline selection. The genes ispB, uppS and metK did not yield recombinants, demonstrating that they are essential genes in all media conditions, while ispA yielded slow-growing recombinants (suggesting that this gene may nevertheless be an “importane” gene according to the invention).
For ispA, ispB, uppsS and metK, the conjugation procedure was also done in the presence of the complementing plasmid pBAD/HisP. This plasmid has both E. coli and Pseudomonas origins of replication, an antibiotic resistance gene for carbenicillin, and an arabinose-inducible copy of the full-length wild-type gene. In this way, recombinants with the chromosomal copies of ispA, ispB, uppS, and metK knocked out could be isolated since the vector copy would provide complementation.
The genes ispB, uppS, and metK are novel with regard to P. aeruginosa. The gene ispB (PA4569, ranging from 5116864 to 5117832 in the genome), has 67% similarity/52% identity to IspB in E. coli, and was assigned to the function class concerned with biosynthesis of cofactors, protein groups and carriers, and energy metabolism, with a confidence level of 2. It is thought to be involved in the pathway of ubiquinone biosynthesis.
The gene uppS (PA3652, ranging from 4091654 to 4090899), coding for undecaprenyl pyrophosphate synthetase, has 69% similarity/57% identity to the uppS gene in E. coli, and was assigned to the function class involved in biosynthesis of cofactors, protein groups and carriers, cell wall and capsule, with a confidence level of 2. It is separated by one gene (cdsA) from dxr, which is involved in the synthesis of isopentenyl diphosphate, a precursor of undecaprenol phosphate.
The gene metK (PA0546, ranging from 604896 to 603706) had never been characterized in P. aeruginosa, although it is 82% similar/72% identical to MetK in E. coli. The gene encodes methionine adenosyltransferase (adomet synthetase) which is involved specifically in methionine metabolism, and was originally assigned to a function class of amino acid biosynthesis and metabolism and central intermediate metabolism with a confidence level of 2.
Example 8
rrF
The essentiality of the P. aeruginosa rrF (PA3653, ranging from 4092227 to 4091670) gene was tested using the promoter swap methodology disclosed herein. The N-terminus region (position 1-327) of the gene encoding the ribosome recycling factor (frr) was cloned into the plasmid vector pBEM10. A single crossover was constructed as described above for lpxC. Recombinants were unable to grow in the absence of arabinose, confiring the essentiality of this gene. The rrf gene encodes ribosome recycling factor, alternatively known as ribosome releasing factor, assigned to the functional class pertaining to translation, post-tanslational modification and degradation with a confidence level of 1. Although this gene was previously known in Pseudomonas aeruginosa, confirming the essentiality of known genes using the methods disclosed herein will reveal new utilities for such genes as targets for the identification and design of new antibacterial drugs.
REFERENCES


    Hardalo, C., Edberg, S. (1991), “Pseudomonas aeruginosa: assessment of risk from drinking water”, Critical Reviews in Microbiology; 23(1), 47-75.
    Stover, K., Pham, X., Erwin, L., Mizoguchi, D., Warrener, P., Hickey, J., Brinkman, S., Hufnagle, W., Kowalik, J., Lagrou, M., Garber, L., Goltry, L., Tolentino, E., Westbrock-Wadman, S., Yuan, Y., Brody, L., Coulter, N., Folger, K, Kas, A., Larbig, K., Lim, R., Smith, K., Spencer, D., Wong, G, Wu, Z., Paulsen, I. (2000), “Complete genome sequence of Pseudomonas aeruginosa PA01, an opportunistic pathogen,” Nature. 406 (6799), 959-964.
    Bodey, G., Bolivar, R., Fainstein, V., Jadeja, L. (1983), “Infections caused by Pseudomonas Aeruginosa,” Reviews of Infectious Diseases, 5(2), 279-313.
    Tummler, B., Bosshammer, J., Breitenstein, S., Brockhausen, I., Gudowius, P., Herrmann, C., Herrmann, S., Heuer, T., Kubesch, P. Mekus, F, Romling, U., Schmidt, K, Spangenberg, C., Walter, S. (1997), “Infections with Pseudomonas aeruginosa in patients with cystic fibrosis,” Behring Institute Mitteilungen, 98 249-55.
    Reznikoff , W. (1993), “The Tn5 Transposon,” Annual Review of Microbiology; 47, 945-63.
    Blumenthal, S., Dayhiya, R. C., and Gross, A. j. (1978), “Estimating the Complete Sample Size from an Incomplete Possion Sample,” Journal of American Statistical Association, 73, 182-187.













TABLE 1







PANumber
GenBank ID
Protein_Name
Gene_Name
Alt_Gene_Name





PA0001
9945819
chromosomal replication initiator protein DnaA
dnaA


PA0004
9945822
DNA gyrase subunit B
gyrB


PA0006
9945824
conserved hypothetical protein

yaeD


PA0008
9945826
glycyl-tRNA synthetase beta chain
glyS


PA0009
9945827
glycyl-tRNA synthetase alpha chain
glyQ


PA0011
9945830
probable 2-OH-lauroyltransferase


PA0015
9945834
hypothetical protein


PA0022
9945841
conserved hypothetical protein

yrdC


PA0026
9945846
hypothetical protein


PA0033
9945854
hypothetical protein


PA0035
9945856
tryptophan synthase alpha chain
trpA


PA0038
9945859
hypothetical protein


PA0039
9945860
hypothetical protein


PA0042
9945864
hypothetical protein


PA0047
9945869
hypothetical protein


PA0052
9945875
hypothetical protein


PA0053
9945876
hypothetical protein


PA0054
9945877
conserved hypothetical protein

yjil


PA0055
9945878
hypothetical protein


PA0058
9945881
hypothetical protein


PA0059
9945882
osmotically inducible protein OsmC
osmC


PA0060
9945883
conserved hypothetical protein


PA0061
9945884
hypothetical protein


PA0065
9945889
hypothetical protein


PA0068
9945892
hypothetical protein


PA0069
9945893
conserved hypothetical protein


PA0070
9945894
hypothetical protein


PA0080
9945905
hypothetical protein


PA0082
9945907
hypothetical protein


PA0094
9945920
hypothetical protein


PA0098
9945924
hypothetical protein


PA0100
9945926
hypothetical protein


PA0105
9945932
cytochrome c oxidase, subunit II
coxB
coll


PA0109
9945936
hypothetical protein


PA0111
9945938
hypothetical protein


PA0113
9945940
probable cytochrome c oxidase assembly factor


PA0114
9945941
conserved hypothetical protein


PA0115
9945942
conserved hypothetical protein

elaA


PA0116
9945944
hypothetical protein


PA0119
9945947
probable dicarboxylate transporter


PA0120
9945948
probable transcriptional regulator


PA0124
9945952
hypothetical protein


PA0125
9945953
hypothetical protein


PA0128
9945956
conserved hypothetical protein

phnA


PA0131
9945960
hypothetical protein


PA0133
9945962
probable transcriptional regulator


PA0135
9945964
hypothetical protein


PA0139
9945969
alkyl hydroperoxide reductase subunit C
ahpC


PA0143
9945973
probable nucleoside hydrolase


PA0145
9945975
hypothetical protein


PA0149
9945980
probable sigma-70 factor, ECF subfamily


PA0154
9945985
protocatechuate 3,4-dioxygenase alpha subun
pcaG


PA0159
9945991
probable transcriptional regulator


PA0161
9945993
hypothetical protein


PA0167
9945999
probable transcriptional regulator


PA0170
9946003
hypothetical protein


PA0171
9946004
hypothetical protein


PA0182
9946016
probable short-chain dehydrogenase

yjgl


PA0183
9946017
arylsulfatase
atsA


PA0184
9946018
probable ATP-binding component of ABC trans

atsC


PA0187
9946021
hypothetical protein


PA0188
9946022
hypothetical protein


PA0200
9946035
hypothetical protein


PA0202
9946037
probable amidase


PA0203
9946038
probable binding protein component of ABC tra


PA0204
9946039
probable permease of ABC transporter


PA0205
9946040
probable permease of ABC transporter


PA0207
9946042
probable transcriptional regulator


PA0209
9946045
conserved hypothetical protein

mdcB


PA0211
9946047
malonate decarboxylase beta subunit
mdcD


PA0213
9946049
hypothetical protein

mdcG


PA0216
9946052
probable transporter

madM


PA0233
9946071
probable transcriptional regulator


PA0236
9946074
probable transcriptional regulator


PA0238
9946076
hypothetical protein


PA0243
9946082
probable transcriptional regulator


PA0244
9946083
hypothetical protein


PA0245
9946084
3-dehydroquinate dehydratase
aroQ2
aroD2


PA0250
9946090
conserved hypothetical protein


PA0251
9946091
hypothetical protein


PA0258
9946098
hypothetical protein


PA0260
9946101
hypothetical protein


PA0261
9946102
hypothetical protein


PA0264
9946105
hypothetical protein


PA0273
9946115
probable MFS transporter


PA0279
9946122
probable transcriptional regulator

ydfF


PA0280
9946123
sulfate transport protein CysA
cysA


PA0284
9946127
hypothetical protein


PA0309
9946155
hypothetical protein


PA0311
9946157
hypothetical protein


PA0320
9946167
conserved hypothetical protein


PA0330
9946178
ribose 5-phosphate isomerase
rpiA


PA0332
9946180
hypothetical protein


PA0336
9946184
conserved hypothetical protein

ygdP


PA0339
9946187
hypothetical protein


PA0341
9946190
prolipoprotein diacyglycetyl transferase
lgt
umpA


PA0342
9946191
thymidylate synthase
thyA


PA0350
9946200
dihydrofolate reductase
folA
tmrA


PA0358
9946208
hypothetical protein


PA0362
9946213
ferredoxin [4Fe-4S]
fdx1


PA0363
9946214
phosphopantetheine adenylyltransferase
coaD
kdtB


PA0369
9946220
hypothetical protein


PA0370
9946222
conserved hypothetical protein

yhhF


PA0373
9946225
signal recognition particle receptor FtsY
ftsY


PA0376
9946228
sigma factor RpoH
rpoH


PA0377
9946229
hypothetical protein


PA0380
9946232
conserved hypothetical protein


PA0384
9946237
hypothetical protein


PA0398
9946252
hypothetical protein


PA0402
9946256
aspartate carbamoyltransferase
pyrB


PA0403
9946257
transcriptional regulator PyrR
pyrB


PA0404
9946258
conserved hypothetical protein

yqgF


PA0405
9946259
conserved hypothetical protein

yqgE


PA0407
9946262
glutathione synthetase
gshB


PA0412
9946267
methyltransferase PilK
pilK


PA0416
9946271
probable transcriptional regulator

chpD


PA0422
9946278
conserved hypothetical protein


PA0427
9946283
outer membrane protein OprM precursor
oprM


PA0433
9946290
hypothetical protein


PA0442
9946300
hypothetical protein


PA0443
9946301
probable transporter


PA0445
9946304
probable transposase


PA0446
9946305
conserved hypothetical protein


PA0448
9946307
probable transcriptional regulator


PA0453
9946312
hypothetical protein


PA0456
9946316
probable cold-shock protein


PA0466
9946327
hypothetical protein


PA0474
9946336
hypothetical protein


PA0475
9946337
probable transcriptional regulator


PA0477
9946339
probable transcriptional regulator


PA0479
9946341
probable transcriptional regulator


PA0488
9946351
conserved hypothetical protein

yfiM


PA0489
9946352
probable phosphoribosyl transferase


PA0490
9946353
hypothetical protein


PA0493
9946356
probable biotin-requiring enzyme


PA0498
9946362
hypothetical protein


PA0501
9946365
8-amino-7-oxononanoate synthase
bioF


PA0502
9946366
probable biotin biosynthesis protein bioH

bioH


PA0503
9946367
probable biotin synthesis protein BioC

bioC


PA0504
9946368
dethiobiotin synthase
bioD


PA0505
9946369
hypothetical protein


PA0514
9946379
heme d1 biosynthesis protein NirL
nirL


PA0527
9946393
transcriptional regulator Dnr
dnr


PA0531
9946397
probable glutamine amidotransferase


PA0535
9946402
probable transcriptional regulator


PA0540
9946407
hypothetical protein


PA0542
9946409
conserved hypothetical protein

yqjC


PA0543
9946410
hypothetical protein


PA0544
9946411
hypothetical protein


PA0546
9946414
methionine adenosyltransferase
metk


PA0550
9946418
conserved hypothetical protein

ygbM


PA0552
9946420
phosphoglycerate kinase
pgk


PA0553
9946422
hypothetical protein


PA0555
9946424
fructose-1,6-bisphosphate aldolase
fda
fbaA, cbbA, cfxB


PA0559
9946428
conserved hypothetical protein

yhiN


PA0563
9946432
conserved hypothetical protein


PA0565
9946434
conserved hypothetical protein


PA0567
9946437
conserved hypothetical protein

yqaE


PA0570
9946440
hypothetical protein


PA0571
9946441
hypothetical protein


PA0574
9946444
hypothetical protein


PA0578
9946449
conserved hypothetical protein


PA0579
9946450
30S ribosomal protein S21
rpsU


PA0580
9946451
O-sialoglycoprotein endopeptidase
gcp
ygjD


PA0582
9946453
dihydroneopterin aldolase
folB


PA0585
9946456
hypothetical protein


PA0589
9946461
conserved hypothetical protein

glpE


PA0591
9946463
conserved hypothetical protein

apaG


PA0593
9946465
pyridoxal phosphate biosynthetic protein PdxA
pdxA


PA0594
9946466
peptidyl-prolyl cis-trans isomerase SurA
surA


PA0595
9946467
organic solvent tolerance protein OstA precurs
ostA
imp


PA0607
9946481
ribulose-phosphate 3-epimerase
rpe
dod


PA0610
9946484
transcriptional regulator PrtN
prtN


PA0611
9946485
transcriptional regulator PrtR
prtR


PA0613
9946487
hypothetical protein


PA0614
9946488
hypothetical protein


PA0617
9946492
probable bacteriophage protein


PA0626
9946501
hypothetical protein


PA0627
9946502
conserved hypothetical protein


PA0630
9946505
hypothetical protein


PA0632
9946507
hypothetical protein


PA0635
9946511
hypothetical protein


PA0639
9946515
conserved hypothetical protein


PA0642
9946518
hypothetical protein


PA0643
9946519
hypothetical protein


PA0644
9946520
hypothetical protein


PA0646
9946523
hypothetical protein


PA0647
9946524
hypothetical protein


PA0648
9946525
hypothetical protein


PA0652
9946529
transcriptional regulator Vfr
vfr


PA0653
9946530
conserved hypothetical protein

yhfA


PA0655
9946532
hypothetical protein


PA0660
9946538
hypothetical protein


PA0661
9946539
conserved hypothetical protein


PA0665
9946543
conserved hypothetical protein

yadR


PA0678
9946558
probable type II secretion system protein

hxcU


PA0679
9948559
hypothetical protein

hxcP


PA0680
9946560
probable type II secretion system protein

hxcV


PA0684
9946564
probable type II secretion system protein

hxcZ


PA0686
9946566
probable type II secretion system protein

hxcR


PA0687
9946567
probable type II secretion system protein

hxcS


PA0689
9946570
hypothetical protein


PA0697
9946579
hypothetical protein


PA0698
9946580
hypothetical protein


PA0700
9946582
hypothetical protein


PA0702
9946585
hypothetical protein


PA0704
9946587
probably amidase


PA0705
9946588
probable glycosyl transferase

migA


PA0708
9946591
probable transcriptional regulator


PA0709
9946592
hypothetical protein


PA0710
9946593
lactoylglutathione lyase
gloA2


PA0712
9946595
hypothetical protein


PA0714
9946598
hypothetical protein


PA0715
9946599
hypothetical protein


PA0716
9946600
hypothetical protein


PA0717
9946601
hypothetical protein of bacteriophage Pf1


PA0720
9946604
helix destabilizing protein of bacteriophage Pf1


PA0728
9946613
probable bacteriophage integrase


PA0729
9946614
hypothetical protein


PA0730
9946615
probab1e transferase


PA0733
9946618
probable pseudouridylate synthase

rsuA


PA0734
9946619
hypothetical protein


PA0738
9946624
conserved hypothetical protein


PA0742
9946628
hypothetical protein


PA0759
9946647
conserved hypothetical protein


PA0763
9946651
anti-sigma factor MucA
mucA


PA0767
9946655
GTP-binding protein LepA
lepA


PA0768
9946656
signal peptidase I
lepB
lep; SPASE I


PA0771
9946660
GTP-binding protein Era
era


PA0776
9946665
hypothetical protein


PA0778
9946667
hypothetical protein


PA0786
9946676
probable transporter


PA0787
9946677
hypothetical protein


PA0790
9946681
hypothetical protein


PA0802
9946694
hypothetical protein


PA0805
9946697
hypothetical protein


PA0808
9946701
hypothetical protein


PA0815
9946708
probable transcriptional regulator


PA0818
9946712
hypothetical protein


PA0820
9946714
hypothetical protein


PA0822
9946716
hypothetical protein


PA0825
9946719
hypothetical protein


PA0826
9946720
hypothetical protein


PA0829
9946723
probable hydrolase


PA0837
9946732
peptidyl-prolyl cis-trans isomerase SlyD
slyD


PA0850
9946747
hypothetical protein


PA0851
9946748
hypothetical protein


PA0853
9946750
probable oxidoreductase


PA0857
9946754
morphogore protein BolA
bolA


PA0862
9946760
hypothetical protein


PA0867
9946765
hypothetical protein


PA0868
9946766
conserved hypothetical protein

yaeJ


PA0869
9946767
D-alanyl-D-alanine-endopeptidase
pbpG


PA0871
9946770
pterin-4-alpha-carbinolamine dehydratase
phhB


PA0874
9946773
hypothetical protein


PA0880
9946779
probable ring-cleaving dioxygenase


PA0894
9946794
hypothetical protein


PA0900
9946801
hypothetical protein


PA0903
9946804
alanyl-tRNA synthetase
alaS
sya


PA0904
9946806
aspartate kinase alpha and beta chain
lysC
ask; akaB


PA0905
9946807
carbon storage regulator
csrA


PA0906
9946808
probable transcriptional regulator


PA0908
9946810
hypothetical protein


PA0909
9946811
hypothetical protein


PA0913
9946815
probable Mg transporter MgtE
mgtE


PA0922
9946825
hypothetical protein


PA0927
9946831
D-lactate dehydrogenas(fermentative)
IdhA
IdhD


PA0932
9946836
cysteine synthase B
cysM


PA0937
9946842
conserved hypothetical protein

yaiL


PA0939
9946844
hypothetical protein


PA0944
9945849
phosphoribosylaminoimidazole synthetase
purN


PA0945
9946850
phosphoribosylaminoimidazole synthetase
PurM


PA0947
9946853
conserved hypothetical protein


PA0953
9946859
probable thioredoxin

helX


PA0954
9946860
probable acylphosphatase


PA0956
9946862
prolyl-tRNA synthetase
proS


PA0960
9946867
hypothetical protein


PA0962
9946869
probable dna-binding stress protein


PA0969
9946876
TolQ protein
tolQ


PA0970
9946877
TolR protein
tolR


PA0971
9946878
TolA protein
tolA


PA0972
9946879
TolB protein
tolB


PA0973
9946880
outer membrane protein OprL precursor
oprL
pal excC


PA0976
9946884
conserved hypothetical protein


PA0978
9946886
conserved hypothetical protein


PA0979
9946887
conserved hypothetical protein


PA0980
9946888
hypothetical protein


PA0981
9946889
hypothetical protein


PA0983
9946891
conserved hypothetical protein


PA0985
9946893
probable colicin-like toxin


PA0986
9946894
conserved hypothetical protein


PA0990
9946899
conserved hypothetical protein


PA0991
9946900
hypothetical protein


PA0993
9946902
probable pili assembly chaperone


PA1000
9946909
hypothetical protein


PA1006
9946916
conserved hypothetical protein

yrkl


PA1008
9946918
bacterioferritin comigratory protein
bcp


PA1010
9946920
dihydrodipicolinate synthase
dapA


PA1012
9946922
conserved hypothetical protein

yycJ


PA1013
9946923
phosphoribosylaminoimidazole-succinocarbox
purC


PA1021
9946932
probable ehoyl-CoA hydratase/isomerase


PA1026
9946938
hypothetical protein


PA1035
9946948
hypothetical protein


PA1038
9946951
hypothetical protein


PA1039
9946952
conserved hypothetical protein

ychJ


PA1049
9946963
pyridoxine 5′-phosphate oxidase
pdxH


PA1055
9946969
conserved hypothetical protein

phaC


PA1063
9946978
hypothetical protein


PA1068
9946983
probable heat shock protein (hsp90 family)


PA1076
9946992
hypothetical protein


PA1088
9947004
hypothetical protein


PA1089
9947005
conserved hypothetical protein


PA1090
9947006
hypothetical protein


PA1095
9947012
hypothetical protein

fliS


PA1098
9947015
two-component sensor
fleS


PA1102
9947019
flagellar motor switch protein FliG
fliG


PA1105
9947022
flagellar protein FliJ
fliJ


PA1106
9947023
hypothetical protein


PA1107
9947025
conserved hypothetical protein


PA1114
9947032
hypothetical protein


PA1118
9947037
hypothetical protein


PA1120
9947039
conserved hypothetical protein

yfiN


PA1122
9947041
probable peptide deformylase

def, pdf, fms


PA1125
9947044
probable cobalamin biosynthetic protein

cobB


PA1129
9947049
probable fosfomycin resistance protein


PA1134
9947054
hypothetical protein


PA1135
9947055
conserved hypothetical protein

yedU


PA1138
9947058
probable transcriptional regulator


PA1145
9947066
probable transcriptional regulator


PA1149
9947071
hypothetical protein


PA1151
9947073
pyocin S2 immunity protein
imm2


PA1154
9947076
conserved hypothetical protein


PA1155
9947077
ribonucleoside reductase, small chain
nrdB


PA1156
9947078
ribonucleoside reductase, large chain
nrdA


PA1157
9947080
probable two-component response regulator


PA1159
9947082
probable cold-shock protein


PA1160
9947083
hypothetical protein


PA1162
9947085
succinyl-diaminopimelate desuccinylase
dapE


PA1164
9947087
conserved hypothetical protein


PA1165
9947088
hypothetical protein


PA1167
9947091
hypothetical protein


PA1168
9947092
hypothetical protein


PA1172
9947096
cytochrome c-type protein NapC
napC


PA1173
9947097
cytochrome c-type protein NapB precursor
napB


PA1176
9947100
ferredoxin protein NapF
napF


PA1177
9947101
periplasmic nitrate reductase protein NapE
napE


PA1183
9947108
C4-dicarboxylate transport protein
dctA


PA1193
9947119
hypothetical protein


PA1203
9947130
hypothetical protein


PA1204
9947131
conserved hypothetical protein

yieF


PA1206
9947l33
hypothetical protein


PA1213
9947141
hypothetical protein


PA1215
9947143
hypothetical protein


PA1216
9947144
hypothetical protein


PA1217
9947145
probable 2-isopropylmalate synthase


PA1219
9947147
hypothetical protein


PA1223
9947152
probable transcriptional regulator


PA1224
9947153
probable NAD(P)H dehydrogenase


PA1228
9947157
hypothetical protein


PA1230
9947159
hypothetical protein


PA1233
9947162
hypothetical protein


PA1237
9947167
probable multidrug resistance efflux pump


PA1250
9947181
alkaline proteinase inhibitor Aprl
aprl


PA1261
9947193
probable transcriptional regulator


PA1269
9947202
probable transcriptional regulator


PA1280
9947214
hypothetical protein

cobC


PA1285
9947220
probable transcriptional regulator


PA1295
9947231
conserved hypothetical protein

ycgL


PA1298
9947234
conserved hypothetical protein

yohL


PA1300
9947236
probable sigma-70 factor, EGF subfamily


PA1306
9947243
probable HIT family protein


PA1307
9947244
conserved hypothetical protein

yafJ


PA1315
9947252
probable transcriptional regulator


PA1321
9947259
cytochrome o ubiquinol oxidase protein CycE
cyoE


PA1323
9947261
hypothetical protein


PA1328
9947267
probable transcriptional regulator


PA1331
9947270
conserved hypothetical protein

yegH


PA1342
9947282
probable binding protein component of ABC tra


PA1348
9947289
hypothetical protein


PA1349
9947290
conserved hypothetical protein


PA1350
9947291
hypothetical protein


PA1352
9947293
conserved hypothetical protein


PA1353
9947295
hypothetical protein


PA1355
9947297
hypothetical protein


PA1358
9947300
hypothetical protein


PA1362
9947304
hypothetical protein


PA1364
9947306
probable transmembrane sensor


PA1366
9947309
hypothetical protein


PA1369
9947312
hypothetical protein


PA1370
9947313
hypothetical protein


PA1371
9947314
hypothetical protein


PA1372
9947315
hypothetical protein


PA1375
9947319
erythronate-4-phosphate dehydrogenase
pdxB


PA1377
9947321
conserved hypothetical protein

yhhY


PA1378
9947322
hypothetical protein


PA1379
9947323
probable short-chain dehydroenase


PA1394
9947340
hypothetical protein


PA1397
9947343
probable two-component response regulator


PA1398
9947344
hypothetical protein


PA1404
9947351
hypothetical protein


PA1409
9947356
acetylpolyamine aminohydrolase
aphA


PA1426
9947375
hypothetical protein


PA1427
9947376
hypothetical protein


PA1431
9947380
regulatory protein RsaL
rsaL


PA1432
9947381
autoinducer synthesis protein LasI
lasI


PA1442
9947393
conserved hypothetical protein

fliL


PA1447
9947398
flagellar biosynthetic protein FliQ
fliQ


PA1454
9947406
flagellar synthesis regulator FleN


PA1456
9947408
two-component response regulator CheY
cheY


PA1461
9947413
probable chemotaxis protein

motB


PA1462
9947414
probable plasmid partitioning protein


PA1464
9947417
Probable purine-binding chemotaxis protein

cheW


PA1465
9947418
hypothetical protein


PA1468
9947421
hypothetical protein


PA1472
9947425
conserved hypothetical protein


PA1475
9947428
heme exporter protein CcmA
ccmA
#NAME?


PA1476
9947429
heme exporter protein CcmB
ccmB
cyt10; cycW; helB


PA1477
9947431
heme exporter protein CcmC
ccrnC
pfcyt1 cycZ helC


PA1478
9947432
hypothetical protein

pfcyt2 ccmD cycX helD


PA1480
9947434
cytochrome C-type biogenesis protein CcmF
ccmF
cyck; ccl1


PA1481
9947435
cytochrome C biogenesis protein CcmG
ccmG
dsbE


PA1482
9947436
cytochrome C-type biogenesis protein CcmH
ccmH
ccl2 cycL


PA1488
9947442
hypothetical protein


PA1489
9947443
hypothetical protein


PA1492
9947447
hypothetical protein


PA1496
9947451
probable potassium channel


PA1504
9947460
probable transcriptional regulator


PA1508
9947464
hypothetical protein


PA1509
9947465
hypothetical protein


PA1514
9947471
conserved hypothetical protein

ybbT


PA1517
9947474
conserved hypothetical protein


PA1518
9947475
conserved hypothetical protein


PA1526
9947484
probable transcriptional regulator


PA1528
9947486
cell division protein ZipA
zipA


PA1529
9947487
DNA ligase
lig
dnaL ligA


PA1532
9947490
DNA polymerase subunits gamma and tau
dnaX


PA1533
9947491
conserved hypothetical protein


PA1535
9947494
probable acyl-CoA dehydrogenase


PA1533
9947498
hypothetical protein


PA1540
9947499
conserved hypothetical protein


PA1541
9947500
probable drug efflux transporter


PA1548
9947508
conserved hypothetical protein

fixS


PA1551
9947511
probable ferredoxin

fixG


PA1555
9947515
probable cytochrome c

fixP ccoP


PA1558
9947519
hypothetical protein


PA1559
9947520
hypothetical protein


PA1560
9947521
hypothetical protein


PA1564
9947526
conserved hypothetical protein


PA1568
9947530
conserved hypothetical protein


PA1571
9947533
hypothetical protein


PA1581
9947544
succinate dehydrogenase (C subunit)
sdhC
cybA


PA1582
9947545
succinate dehydrogenase (D subunit)
sdhD


PA1583
9947546
succinate dehydrogenase (A subunit)
sdhA


PA1584
9947547
succinate dehydrogenase (B subunit)
sdhB


PA1587
9947550
lipoamide dehydrogenase-glc
lpdG
lpdA


PA1588
9947552
succinyl-CoA synthetase beta chain
sucC


PA1589
9947553
succinyl-CoA synthetase alpha chain
sucD


PA1591
9947555
hypothetical protein


PA1592
9947556
hypothetical protein


PA1593
9947557
hypothetical protein


PA1594
9947558
hypothetical protein


PA1595
9947559
hypothetical protein


PA1610
9947576
beta-hydroxydecanoyl-ACP dehydrase
fabA


PA1618
9947584
conserved hypothetical protein

ybdB


PA1619
9947585
probable transcriptional regulator


PA1622
9947589
probable hydrolase


PA1623
9947590
conserved hypothetical protein


PA1624
9947591
hypothetical protein


PA1630
9947597
probable transcriptional regulator


PA1632
9947600
KdpF protein
kdpF


PA1635
9947603
potassium-transporing ATPase, C chain
kdpC
atkC


PA1638
9947606
conserved hypothetical protein

yneH


PA1641
9947610
hypothetical protein


PA1645
9947614
hypothetical protein


PA1657
9947627
conserved hypothetical protein


PA1664
9947635
hypothetical protein


PA1666
9947637
hypothetical protein


PA1673
9947645
hypothetical protein


PA1674
9947646
GTP cyclohydrolase I precursor
folE2


PA1675
9947647
conserved hypothetical protein


PA1676
9947648
hypothetioal protein


PA1687
9947660
spermidine synthase
speE


PA6909
9947663
translocation protein in type III secretion
pscU


PA1691
9947664
translocation protein in type III secretion
pscT


PA1696
9947669
translocation protein in type III secretion
pscO


PA1698
9947672
outer membrane protein PopN
popN


PA1701
9947675
conserved hypothetical protein in type III secretion

pcr3


PA1702
9947676
conserved hypothetical protein in type III secretion

pcr4


PA1705
9947679
regulator in type III secretion
pcrG


PA1710
9947684
exoenzyme S synthesis protein C precursor
exsC


PA1711
9947685
hypothetical protein


PA1718
9947693
type III export protein PscE
pscE


PA1719
9947694
type III export protein PscF
pscF


PA1720
9947695
type III export protein PscG
pscG


PA1722
9947697
type III export protein Pscl
pscl


PA1732
9947708
conserved hypothetical protein


PA1733
9947709
conserved hypothetical protein


PA1743
9947720
hypothetical protein


PA1745
9947722
hypothetical protein


PA1747
9947725
hypothetical protein


PA1750
9947728
phospho-2-dehydro-3-deoxyheptonate aldolase


PA1757
9947735
homoserine kinase
thrH


PA1768
9947747
hypothetical protein


PA1772
9947752
probable methyltransferase

menG


PA1777
9947757
outer membrane protein OprF precursor
oprF


PA1780
9947760
assimilatory nitrite reductase small subunit
nirD
nasE


PA1783
9947764
nitrate transporter
nasA
nasT


PA1785
9947766
conserved hypothetical protein

nasT


PA1787
9947768
aconitate hydratase 2
acnB


PA1790
9947772
hypothetical protein


PA1792
9947774
conserved hypothetical protein

ybbF


PA1794
9947776
glutaminyl-tRNA synthetase
glnS


PA1795
9947777
cysteinyl-tRNA synthetase
cysS


PA1796
9947778
5,10-methylene-tetrahydrofolate dehydrogena
folD


PA1803
9947786
Lon protease
lon
capR deg muc lopA


PA1815
9947800
ribonuclease H
rnhA


PA1816
9947801
DNA polymerase III, epsilon chain
dnaQ
mutD


PA1817
9947802
hypothetical protein


PA1820
9947805
sodium/proton antiporter NhaB

nhaB


PA1825
9947811
hypothetical protein


PA1830
9947816
hypothetical protein


PA1835
9947821
hypothetical protein


PA1837
9947823
hypothetical protein


PA1840
9947827
hypothetical protein


PA1842
9947829
hypothetical protein


PA1845
9947832
hypothetical protein


PA1847
9947835
conserved hypothetical protein

yhgl


PA1852
9947840
hypothetical protein


PA1855
9947843
hypothetical protein


PA1859
9947848
probable transcriptional regulator


PA1862
9947851
molybdenum transport protein ModB
modB


PA1867
9947857
hypothetical protein

xphA


PA1869
9947859
probable acyl carrier protein


PA1872
9947862
hypothetical protein


PA1882
9947873
probable transporter


PA1883
9947874
probable NADH-ubiquinone/plastoquinone oxid


PA1884
9947875
probable transcriptional regulator


PA1885
9947876
conserved hypothetical protein


PA1892
9947884
hypothetical protein


PA1894
9947886
hypothetical protein


PA1895
9947887
hypothetical protein


PA1896
9947788
hypothetical protein


PA1897
9947789
hypothetical protein


PA1899
9947892
probable phenazine biosynthesis protein

phzA2


PA1900
9947893
probable phenazine biosynthesis protein

phzB2


PA1905
9950429
probable pyridoxamine 5′-phosphate oxidase

phzG2


PA1911
9947904
probable transmembrane sensor


PA1912
9947905
probable sigma-70 factor, ECF subfamily


PA1914
9947907
conserved hypothetical protein

hvn


PA1917
9947910
hypothetical protein


PA1924
9947918
hypothetical protein


PA1925
9947919
hypothetical protein


PA1928
9947923
ribosomal protein alanine acetyltransferase
rimJ


PA1929
9947924
hypothetical protein


PA1936
9947932
hypothetical protein


PA1937
9947933
conserved hypothetical protein


PA1938
9947934
conserved hypothetical protein


PA1939
9947935
hypothetical protein


PA1951
9947949
hypothetical protein


PA1952
9947950
hypothetical protein


PA1955
9947953
hypothetical protein


PA1956
9947954
hypothetical protein


PA1962
9947960
conserved hypothetical protein


PA1963
9947962
hypothetical protein


PA1965
9947964
hypothetical protein


PA1967
9947966
hypothetical protein


PA1968
9947967
hypothetical protein


PA1974
9947974
hypothetical protein


PA1978
9947978
probable transcriptional regulator

agmR


PA1980
9947980
probable two-component response regulator


PA1985
9947986
pyrroloquinoline quinone biosynthesis protein A
pqqA


PA1986
9947987
pyrroloquinoline quinone biosynthesis protein B
pqqB


PA1988
9947989
pyrroloquinoline quinone biosynthesis protein D
pqqD


PA1994
9947996
hypothetical protein


PA1995
9947997
hypothetical protein 


PA1996
9947998
peptidyl-prolyl cis-trans isomerase C1
ppiC1


PA2001
9948003
acetyl-CoA acetyltransferase
atoB


PA2002
9948004
conserved hypothetical protein

atoE


PA2007
9948010
maleylacetoacetate isomerase
maiA


PA2010
9948013
probable transcriptional regulator


PA2013
99480l6
probable enoyl-CoA hydratase/isomerase

menB


PA2015
9948019
probable acyl-CoA dehydrogenase


PA2016
9948020
probable transcriptional regulator


PA2017
9948021
hypothetical protein


PA2021
9948025
hypothetical protein


PA2026
9948031
conserved hypothetical protein

yfeH


PA2029
9948034
hypothetical protein


PA2031
9948036
hypothetical protein


PA2034
9948039
hypothetical protein


PA2037
9948043
hypothetical protein


PA2042
9948048
probably transporter (membrane subunit)

ygjU


PA2051
9948058
probable transmembrane sensor


PA2052
9948059
cyanate lyase
cynS


PA2060
9948068
probable permease of ABC transporter


PA2062
9948071
probable pyridoxal-phosphate dependent enzy


PA2066
9948075
hypothetical protein


PA2071
9948081
elongation factor G
fusA2


PA2073
9948083
probable transporter (membrane subunit)


PA2074
9948084
hypothetical protein


PA2075
9948086
hypothetical protein


PA2080
9948091
hypothetical protein


PA2088
9948100
hypothetical protein


PA2090
9948102
hypothetical protein


PA2092
9948104
probable MFS transporter


PA2095
9948108
hypothetical protein


PA2097
9948110
probable flavin-binding monooxygenase


PA2101
9948114
conserved hypothetical protein


PA2103
9948117
probable molybdopterin biosynthesis protein MoeB

moeB


PA2105
9948119
probable acetyltransferase


PA2107
9948121
hypothetical protein


PA2110
9948124
hypothetical protein


PA2118
9948133
O6-methylguanine-DNA methyltransferase
ada


PA2119
9948134
alcohol dehydrogenase (Zn-dependent)

adh


PA2120
9948135
hypothetical protein


PA2123
9948138
probable transcriptional regulator


PA2126
9948142
conserved hypothetical protein


PA2131
9948147
hypothetical protein


PA2136
9948153
hypothetical protein


PA2142
9948159
probable short-chain dehydrogenase

yhxC


PA2143
9948160
hypothetical protein


PA2146
9948164
conserved hypothetical protein

yciG


PA2149
9948167
hypothetical protein


PA2157
9948175
hypothetical protein


PA2161
9948180
hypothetical protein


PA2166
9948186
hypothetical protein


PA2167
9948187
hypothetical protein


PA2170
9948190
hypothetical protein


PA2171
9948191
hypothetical protein


PA2174
9948194
hypothetical protein


PA2175
9948195
hypothetical protein


PA2182
9948203
hypothetical protein


PA2183
9948204
hypothetical protein


PA2184
9948205
conserved hypothetical protein

yciE


PA2185
9948206
hypothetical protein


PA2186
9948207
hypothetical protein


PA2187
9948208
hypothetical protein


PA2190
9948211
conserved hypothetical protein


PA2192
9948214
conserved hypothetical protein


PA2196
9948218
probable transcriptional regulator


PA2197
9948219
conserved hypothetical protein

ycnB


PA2205
9948228
hypothetical protein


PA2207
9948230
hypothetical protein


PA2211
9948234
conserved hypothetical protein


PA2214
9948238
probable MFS transporter


PA2219
9948243
membrane protein OpdE
opdE


PA2220
9948244
probable transcriptional regulator

opdR


PA2221
9948245
conserved hypothetical protein


PA2222
9948247
hypothetical protein


PA2223
9948248
hypothetical protein


PA9948
9948249
hypothetical protein


PA2225
9948250
hypothetical protein


PA2226
9948251
hypothetical protein


PA2227
9948252
probable transcriptional regulator


PA2228
9948253
hypothetical protein


PA2229
9948254
conserved hypothetical protein

yiiM


PA2234
9948259
probable exopolysaccharide transporter


PA2242
9948268
hypothetical protein


PA2245
9948271
hypothetical protein


PA2251
9948278
hypothetical protein


PA2253
9948280
L asparaginase I
ansA


PA2257
9948284
pyoverdine biosynthesis protein PvcD
pvcD


PA2258
9948285
transcriptronai regulator PtXR
ptxR


PA2260
9948288
hypothetical protein


PA2280
9948309
conserved hypothetical protein

arsH


PA2282
9948312
hypothetical protein


PA2284
9948314
hypothetical protein


PA2292
9948323
hypothetical protein


PA2293
9948324
hypothetical protein


PA2294
9948325
probable ATP-binding component of ABC trans


PA2295
9948326
probable permease of ABC transporter


PA2297
9948328
probable ferredoxin


PA2298
9948329
probable oxidoreductase


PA2303
9948335
hypothetical protein


PA2311
9948344
hypothetical protein


PA2316
9948349
probable transcriptional regulator


PA2329
9948364
probable ATP-binding component of ABC trans


PA2331
9948366
hypothetical protein


PA2336
9948371
hypothetical protein


PA2338
9948374
probable binding protein component of ABC m

mtlE


PA2343
9948379
xylulose kinase
mtlY


PA2347
9948384
hypothetical protein


PA2349
9948386
conserved hypothetical protein


PA2351
9948388
probable permease of ABC transporter


PA2365
9948403
conserved hypothetical protein


PA2367
9948406
hypothetical protein


PA2368
9948407
hypothetical protein


PA2370
9948409
hypothetical protein


PA2372
9948411
hypothetical protein


PA2375
9948414
hypothetical protein


PA2383
9948423
probable transcriptional regulator


PA2391
9948432
probable outer membrane protein


PA2405
9948449
hypothetical protein


PA2406
9948450
hypothetical protein


PA2411
9948455
probable thioesterase


PA2412
9948456
conserved hypothetical protein


PA2418
9948463
hypothetical protein


PA2422
9948467
hypothetical protein


PA2427
9948473
hypothetical protein


PA2428
9948474
hypothetical protein


PA2429
9948475
hypothetical protein


PA2434
9948480
hypothetical protein


PA2436
9948482
hypothetical protein


PA2441
9948488
hypothetical protein


PA2442
9948489
glycine cleavage system protein T2
gcvT2


PA2446
9948494
glycine cleavage system protein H2
gcvH2


PA2451
9948499
hypothetical protein


PA2453
9948502
hypothetical protein


PA2455
9948504
hypothetical protein


PA2456
9948505
hypothetical protein


PA2459
9948508
hypothetical protein


PA2460
9948509
hypothetical protein


PA2461
9948510
hypothetical protein


PA2464
9948514
hypothetical protein


PA2467
9948517
probable transmembrane sensor


PA2469
9948519
probable transcriptional regulator


PA2473
9948524
probable glutathione S-transferase


PA2474
9948525
hypothetical protein


PA2475
9948526
probable cytochrome P450


PA2485
9948537
hypothetical protein


PA2487
9948539
hypothetical protein


PA2490
9948542
conserved hypothetical protein

ydbB


PA2491
9948543
probable oxidoreductase


PA2492
9948544
transcriptional regulator MexT
mexT


PA2496
9948549
hypothetical protein


PA2500
9948553
probable MFS transporter

cynX


PA2501
9948554
hypothetical protein


PA2504
9948557
hypothetical protein


PA2507
9948561
catechol 1,2-dioxygenase
catA


PA2515
9948569
cis-1,2-dihydroxycyclohexa-3,4-diene carboxyl
axylL


PA2517
9948571
toluate 1,2-dioxygenase beta subunit
xylY


PA2521
9948576
RND divalent metal cation efflux membrane fu
czcB


PA2536
9948593
probable phosphatidate cytidylyltransferase

ynbB


PA2538
9948595
hypothetical protein


PA2539
9948596
conserved hypothetical protein

ynbD


PA2544
9948602
hypothetical protein


PA2549
9948608
conserved hypothetical protein

ygjT


PA2561
9948610
probable transcriptional regulator


PA2552
9948611
probable acyl-CoA dehydrogenase

acdB


PA2553
9948612
probable acyl-CoA thiolase


PA2554
9948613
probable short-chaindehydrogenase


PA2577
9948639
probable transcriptional regulator


PA2584
9948647
CDP-diacylglycerol-glycerol-3-phosphate-3-ph
pgsA


PA2591
9948655
probable transcriptional regulator


PA2602
9948667
hypothetical protein


PA2605
9948670
conserved hypothetical protein

yheN


PA2606
9948671
conserved hypothetical protein

yheM


PA2607
9948672
consented hypothetical protein


PA2608
9948673
conserved hypothetical protein

yccK


PA2612
9948677
seryl tRNA synthetase
serS


PA2614
9948680
periplasmic chaperone LolA
lolA


PA2615
9948681
cell division protein FtsK
ftsK


PA2617
9948683
leucyl/phenylalanyl-tRNA-protein transferase
aat


PA2619
9948685
initiation factor
infA


PA2621
9948687
conserved hypothetical protein


PA2626
9948693
tRNA methyltransferase
trmU
asuE


PA2629
9948696
adenylosuccinate lyase
purB


PA2638
9948706
NADH dehydrogenase I chain B
nuoB


PA2641
9948709
NADH dehydrogenase I chain F
nuoF


PA2645
9948714
NADH dehydrogenase I chain J
nuoJ


PA2646
9948715
NADH dehydrogenase I chain K
nuoK


PA2658
9948728
hypothetical protein


PA2663
9948734
hypothetical protein


PA2666
9948737
probable 6-pyruvoyl tetrahydrobiopterin syntha

ptpS


PA2667
9948738
conserved hypothetical protein


PA2668
9948739
hypothetical protein


PA2673
9948744
probable type II secretion system protein

hplV


PA2674
9948745
probable type II secretion system protein

hplU


PA2675
9948746
probable type II secretion system protein

hplT


PA2678
9948749
probable permease of ABC-2 transporter


PA2681
9948753
probable transcriptional regulator


PA2683
9948755
probable serine/threonine dehydratase, degrad

tdcB


PA2689
9948762
hypothetical protein


PA2690
9948763
probable transposase


PA2694
9948767
probable thioredoxin


PA2697
9948771
hypothetical protein


PA2703
9948777
hypothetical protein


PA2706
9948780
hypothetical protein


PA2715
9948790
probable ferredoxin


PA2719
9948795
hypothetical protein


PA2720
9948796
hypothetical protein


PA2721
9948797
hypothetical protein


PA2722
9948798
hypothetical protein


PA2723
9948799
hypothetical protein


PA2726
9948802
probable radical activating enzyme


PA2730
9948807
hypothetical protein


PA2731
9948808
hypothetical protein


PA2733
9948810
conserved hypothetical protein


PA2734
9948811
hypothetical protein


PA2736
9948814
hypothetical protein


PA2737
9948815
conserved hypothetical protein


PA2738
9948816
integration host factor, alpha subunit
himA


PA2739
9948817
phenylalanyl-tRNA synthetase, beta subunit
pheT


PA2740
9948818
phenylalanyl-tRNA synthetase, alpha-subunit
pheS


PA2741
9948819
50S ribosomal protein L20
rplT


PA2742
9948820
50S ribosomal protein L35
rpml


PA2743
9948821
translation initiation factor IF-3
infC


PA2744
9948822
threonyl tRNA synthetase
thrS


PA2749
9948828
DNA-specific endonuclease I
endA


PA2753
9948832
hypothetical protein


PA2758
9948835
hypothetical protein


PA2759
9948839
hypothetical protein


PA2762
9948842
hypothetical protein


PA2763
9948843
hypothetical protein


PA2767
9948847
probable enoyl-CoA hydratase/isomerase


PA2768
9948848
hypothetical protein


PA2769
9948849
hypothetical protein


PA2774
9948855
hypothetical protein


PA2775
9948856
hypothetical protein


PA2780
9948861
hypothetical protein


PA2781
9948862
hypothetical protein


PA2782
9948863
hypothetical protein


PA2784
9948866
hypothetical protein


PA2785
9948867
conserved hypothetical protein


PA2786
9948868
hypothetical protein


PA2792
9948874
hypothetical protein


PA2794
9948877
hypothetical protein


PA2797
9948880
hypothetical protein


PA2799
9948882
hypothetical protein


PA2800
9948883
conserved hypothetical protein

vacJ


PA2803
9948886
hypothetical protein


PA2805
9948888
hypothetical protein


PA2807
9948891
hypothetical protein


PA2808
9948892
hypothetical protein


PA2811
9948895
probable permease of ABC-2 transporter

yadH


PA2818
9948902
hypothetical protein


PA2819
9948903
hypothetical protein


PA2827
9948912
conserved hypothetical protein

yeaA


PA2829
9948914
hypothetical protein


PA2831
9948917
conserved hypothetical protein


PA2832
9948918
thiopurine methyltransferase
tpm


PA2839
9948925
conserved hypothetical protein

ygiD


PA2843
9948930
probable aldolase


PA2845
9948932
hypothetical protein


PA2851
9948938
translation elongation factor P
efp


PA2852
9948939
hypothetical protein


PA2853
9948941
outer membrane lipoprotein Oprl precursor
oprl


PA2854
9948942
conserved hypothetical protein

erfK


PA2859
9948947
transcription elongation factor GreB
greB


PA2863
9948951
lipase modulator protein
lipH


PA2868
9948957
hypothetical protein


PA2874
9948963
hypothetical protein


PA2876
9948966
orotidine 5′-phosphate decarboxylase
pyrF


PA2877
9948967
probable transcriptional regulator


PA2879
9948969
probable transcriptional regulator

hpkR


PA2883
9948973
hypothetical protein


PA2894
9948985
hypothetical protein


PA2898
9948990
hypothetical protein


PA2901
9948993
hypothetical protein


PA2910
9949003
conserved hypothetical protein

yebN


PA2915
9949008
hypothetical protein


PA2916
9949010
hypothetical protein


PA2922
9949016
probable hydrolas


PA2928
9949023
hypothetical protein


PA2935
9949030
hypothetical protein


PA2936
9949031
hypothetical protein


PA2936
9949033
hypothetical protein


PA2940
9949036
probable acyl-CoA thiolase


PA2949
9949046
probable lipase


PA2951
9949048
electron transfer flavoprotein alpha-subunit
etfA


PA2952
9949049
electron transfer flavoprotein beta-subunit
etfB


PA2953
9949050
electron transfer flavoprotein-ubiquinone oxido


PA2960
9949058
type 4 fimbrial biogenesis protein PilZ
pilZ


PA2961
9949059
DNA polymerase Ill, delta prime subunit
holB


PA2962
9949060
thymidylate kinase
tmk


PA2963
9949061
conserved hypothetical protein

yceG


PA2966
9949064
acyl carrier protein
acpP


PA2967
9949065
3 oxoacyl-[acyl-carrier-protein] reductase
fabG


PA2968
9949066
malonyl-CoA-[acyl-carrier-protein] transacylase
fabD


PA2970
9949069
50S ribosomal protein L32
rpmF


PA2971
9949070
conserved hypothetical protein

yceD


PA2975
9949074
ribosomal large subunit pseudouridine synthas
rluC
yceC


PA2977
9949076
UDP-N-acetylpyruvoylglucosamine reductase
murB


PA2978
9949077
phosphotyrosine protein phosphatase
ptpA


PA2979
9949078
3-deoxy-manno-octulosonate cytidylyltransfer
kdsB


PA2980
9949079
conserved hypothetical protein

ycaR


PA2981
9949080
tetraacyldisaccharide 4*-kinase
lpxK


PA2982
9949081
conserved hypothetical protein


PA2983
9949082
probable tolQ-type transport protein


PA2985
9949085
hypothetical protein


PA2988
9949086
conserved hypothetical protein


PA2987
9949087
probable ATP-binding component of ABC trans

ycfV


PA2988
9949088
conserved hypothetical protein


PA2989
9949089
hypothetical protein


PA2991
9949091
soluble pyridine nucleotide transhydrogenase
sth


PA2992
9949092
hypothetical protein


PA2996
9949096
Na+-translocating NADH: uniquinone oxidoredu
nqrD


PA3001
9949102
probable glyceraldehyde-3-phosphate dehydro


PA3004
9949105
probable nucleoside phosphorylase


PA3009
9949111
hypothetical protein


PA3011
9949113
DNA topoisomerase I
topA


PA3012
9949114
hypothetical protein


PA3017
9949120
conserved hypothetical protein


PA3021
9949124
hypothetical protein


PA3022
9949125
hypothetical protein


PA3024
9949127
probable carbohydrate kinase


PA3030
9949134
probable molybdopterin-guanine dinucleotide b

mobA


PA3033
9949137
hypothetical protein


PA3036
9949140
hypothetical protein


PA3040
9949145
conserved hypothetical protein

yqjD


PA3041
9949146
hypothetical protein

yqjE


PA3042
9949147
hypothetical protein


PA3046
9949151
conserved hypothetical protein

yggL


PA3049
9949155
ribosome modulation factor
rmf


PA3051
9949157
hypothetical protein


PA3067
9949174
probable transcriptional regulator


PA3081
9949189
conserved hypothetical protein


PA3086
9949193
hypothetical protein


PA3088
9949197
conserved hypothetical protein

vfjB


PA3089
9949198
hypothetical protein


PA3093
9949202
hypothetical protein


PA3095
9949205
general secretion pathway protein M
xcpZ


PA3096
9949206
general secretion pathway protein L
xcpY


PA3100
9949210
general secretion pathway protein H
xcpU
pddB


PA3103
9949213
general secretion pathway protein E
xcpR


PA3110
9949221
hypothetical protein


PA3112
9949223
acetyl CoA carboxylase beta subunit
accD
dedB


PA3117
9949229
aspartate semialdehyde dehydrogenase
asd


PA3123
9949235
conserved hypothetical protein


PA4314
9949254
hypothetical protein


PA3142
9949256
hypothetical protein


PA3144
9949256
hypothetical protein


PA3145
9949259
glycosyltransferase WbpL
wbpL


PA3146
9949260
probable NAD-dependent epimerase/dehydrate
wbpK


PA3147
9949261
probable glycosyl transferase WbpJ
wbpJ


PA3148
9949262
probable UDP-N-acetylglucosamine 2-epimera
wbpl


PA3149
9949263
probable glycosyltransferase WbpH
wbpH


PA3150
9949264
LPS biosynthesis protein WbpG
wbpG


PA3151
9949266
imidazoleglycerol-phosphate synthase, cyclase
hisF2


PA3152
9949267
glutamine amidotransferase
hisH2


PA3153
9949268
O-antigen translocase
wzx
wbpF, rfbX


PA3154
9949269
B-band O-antigen polymerase
wzy
rfc


PA3165
9949270
probab1e aminotransferase WbpE
wbpE


PA3156
9949271
probable acetyltransferase WbpD
wbpD


PA3157
9949272
probable acetyltransferase

wbpC


PA3158
9949273
probable oxidoreductase WpbB
wbpB


PA3159
9949274
probable UDP-glucose/GDP-mannose dehydro
wbpA


PA3160
9949276
O-antigen chain length regulator
wzz
cld, rol


PA3161
9949277
integration host factor beta subunit
himD


PA3162
9949278
30S ribosoml protein S1
rpsA


PA3163
9949279
cytidylate kinase
cmk


PA3167
9949283
3-phosphoserine aminotransferase
serC


PA3168
9949285
DNA gyrase subunit A
gyrA


PA317T
9949288
3-demethylubiquinone-9 3-methyltransferase
ubiG


PA3178
9949296
hypothetical protein


PA3181
9949299
2-keto-3-deoxy-6-phosphogluconate aldolase

edaA


PA3185
9949303
hypothetical protein


PA3195
9949314
glyceraldehyde 3-phosphate dehydrogenase
gapA


PA3202
9949322
conserved hypothetical protein

ycil


PA3203
9949323
hypothetical protein


PA3207
9949327
hypothetical protein


PA3211
9949331
probable permease of ABC transporter


PA3220
9949341
probable transcriptional regulator


PA3227
9949348
peptidyl-prolyl cis-trans isomerase A
ppiA
cypH


PA3230
9949352
conserved hypothetical protein


PA3232
9949354
probable nuclease


PA3237
9949359
hypothetical protein


PA3242
9949365
probable lauroyl acyltransferase

htrB


PA3245
9949368
cell division topological specificity factor MinE
minE


PA3246
9949369
pseudouridine synthase RluA
rluA
yabO


PA3249
9949372
probable transcriptional regulator


PA3255
9949379
hypothetical protein


PA3260
9949384
probable transcriptional regulator


PA3266
9949391
cold acclimation protein B
capB
cspA


PA3273
9949398
hypothetical protein


PA3274
9949399
hypothetical protein


PA3275
9949401
conserved hypothetical protein

ynfA


PA3278
9949404
hypothetical protein


PA3280
9949406
outer membrane porin OprO precursor
oprO


PA3281
9949407
hypothetical protein


PA3287
9949414
conserved hypothetical protein


PA3288
9949415
hypothetical protein


PA3289
9949416
hypothetical protein


PA3291
9949416
hypothetical protein


PA3292
9949419
hypothetical protein


PA3298
9949426
hypothetical protein


PA3302
9949430
conserved hypothetical protein


PA3309
9949438
conserved hypothetical protein


PA3312
9949441
probable 3-hydroxyisobutyrate dehydrogenase


PA3314
9949443
probable ATP-binding component of ABC trans


PA3315
9949444
probable permease of ABC transporter


PA3317
9949447
hypothetical protein


PA3316
9949448
hypothetical protein


PA3320
9949450
hypothetical protein


PA3326
9949457
probable Clp-family ATP-dependent protease


PA3330
9949461
probable short chain dehydrogenase


PA3332
9949463
conserved hypothetical protein


PA3334
9949465
probable acyl carrier protein


PA3338
9949470
hypothetical protein


PA3341
9949473
probable transcription regulator


PA3347
9949480
hypothetical protein


PA3348
9949481
probable chemotaxis protein methyltransferase

cheR1


PA3351
9949484
hypothetical protein

flgM


PA3353
9949486
hypothetical protein


PA3354
9949487
hypothetical protein


PA3360
9949494
probable secretion protein


PA3367
9949502
hypothetical protein

ydcA


PA3368
9949503
probable acetyltransferase


PA3370
9949505
hypothetical protein


PA3371
9949506
hypothetical protein


PA3380
9949515
conserved hypothetical protein

phnG


PA3384
9949519
ATP binding component of ABC phosphonate
phnC


PA3390
9949525
hypothetical protein


PA3395
9949531
NosY protein
nosY


PA3396
9949532
NosL protein
nosL


PA3397
9949534
ferredoxin—NADP + reductase
fpr


PA3403
9949540
hypothetical protein


PA3407
9949545
heme acquisition protein HasAp
hasAp


PA3413
9949551
conserved hypothetical protein

yebG


PA3414
9949552
hypothetical protein


PA3416
9949554
probable pyruvate dehydrogenase E1 compon


PA3432
9949572
hypothetical protein


PA3433
9949573
probable transcriptional regulator

ywbl


PA3434
9949574
probable transposase


PA3435
9949575
conserved hypothetical protein

mioC


PA3438
9949578
GTP cyclohydrolase I precursor
folE1


PA3459
9949579
d-erythro-7,8-dihydroneopteiln triphosphate
folX


PA3443
9949584
probable permease of ABC transporter

ssuC ycbM


PA3444
9949585
conserved hypothetical protein

ssuD


PA3445
9949586
conserved hypothetical protein


PA3446
9949587
conserved hypothetical protein

ssuE


PA3450
9949591
probable antioxidant protein

lsfA


PA3451
9949592
hypothetical protein


PA3460
9949602
probable acetyltransferase


PA3470
9949614
hypothetical protein


PA3472
9949616
hypothetical protein


PA3477
9949621
transcriptional regulator RhlR
rhlR


PA3482
9949627
methlonyl-tRNA synthetase
metG


PA3488
9949634
hypothetical protein


PA3489
9949635
conserved hypothetical protein

rnfA


PA3492
9949638
conserved hypothetical protein

rnfD


PA3494
9949640
conserved hypothetical protein

rnfE


PA3495
9949641
endonuclease III
nth


PA3496
9949642
hypothetical protein


PA3501
9949647
hypothetical protein


PA3502
9949648
hypothetical protein


PA3505
9949652
hypothetical protein


PA3512
9949659
probable permease of ABC transporter


PA3519
9949667
hypothetical protein


PA3520
9949668
hypothetical protein


PA3523
9949671
probable RND efflux membrane fusion protein


PA3528
9949677
ribonuclease T
rnt


PA3530
9949679
conserved hypothetical protein

bfd


PA3533
9949682
conserved hypothetical protein

ydhD


PA3542
9949693
alginate biosynthesis protein Alg44

alg44


PA3550
9949702
alginate O-acetyltransferase AlgF
algF


PA3558
9949710
hypothetical protein


PA3566
9949719
conserved hypothetical protein

ycnE


PA3570
9949724
methylmalonate-semialdehyde dehydragenase
mmsA


PA3572
9949726
hypothetical protein


PA3575
9949729
hypothetical protein


PA3578
9949732
conserved hypothetical protein


PA3589
9949744
probable acyl-CoA thiolase


PA3600
9949756
conserved hypothetical protein

rpl36


PA3601
9949757
conserved hypothetical protein

ykgM


PA3605
9949762
hypothetical protein


PA3606
9949763
conserved hypothetical protein
yfiP


PA3609
9949766
polyamine transport protein PotC
potC


PA3611
9949768
hypothetical protein


PA3612
9949769
conserved hypothetical protein

ypeB


PA3616
9949774
conserved hypothetical protein

recX


PA3617
9949775
RecA protein
recA


PA3627
9949785
conserved hypothetical protein

ygbB


PA3632
9949791
conserved hypothetical protein

yedF


PA3633
9949792
conserved hypothetical protein

ygbP


PA3634
9949793
conserved hypothetical protein

ybgQ


PA3635
9949794
enolase
eno


PA3636
9949795
2-dehydro-3-deoxyphosphooctonate aldolase
kdsA


PA3637
9949796
CTP synthase
pyrG


PA3638
9949797
conserved hypothetical protein

mesJ


PA3639
9949798
acetyl-coenzyme A carboxylase carboxyl tran
accA


PA3640
9949800
DNA polymerase III, alpha chain
dnaE
polC


PA3643
9949803
lipid A-disaccharide synthase
lpxB
pgsB


PA3644
9949804
UDP-N-acetylglucosamine acyltransferase
lpxA


PA3645
9949805
(3R)-hydroxymyristoyl-[acyl carrier protein] deh
fabZ
sefA


PA3646
9949806
UDP-3-O-[3-hydroxylauroyl] glucosamine N-ac
lpxD
firA omsA


PA3647
9949807
probable outer membrane protein precursor


PA3648
9949808
probable outer membrane protein


PA3650
9949811
1-deoxy-d-xylulose 5-phosphate reductoisome
dxr
yaeM


PA3651
9949812
phosphatidate cytidylyltransferase
cdsA


PA3652
9949813
undecaprenyl pyrophosphate synthetase
uppS
yaeS


PA3653
9949814
ribosome recycling factor
frr
rrf


PA3654
9949815
uridylate kinase
pyrH
smbA


PA3655
9949816
elongation factor Ts
tsf


PA3656
9949817
30S ribosomal protein S2
rpsB


PA3657
9949818
methionine aminopeptidase
map


PA3662
9949824
hypothetical protein


PA3664
9949826
conserved hypothetical protein

yffB


PA3666
9949828
tetrahydrodipicolinate succinylase
dapD


PA3671
9949833
probable permease of ABC transporter


PA3674
9949837
hypothetical protein


PA3678
9949841
probable transcriptional regulator


PA3681
9949844
hypothetical protein


PA3684
9949848
hypothetical protein


PA3685
9949849
conserved hypothetical protein


PA3688
9949852
hypothetical protein


PA3893
9949858
conserved hypothetical protein


PA3701

peptide chain release factor 2
prfB


PA3704
9949868
probable chemotaxis sensor/effector fusion pro


PA3719
9949885
hypothetical protein


PA3725
9949891
single-stranded-DNA-specific exonuclease Re
recJ


PA3726
9949892
conserved hypothetical protein

yaeQ


PA3730
9949897
hypothetical protein


PA3731
9949898
conserved hypothetical protein

yjfJ


PA3733
9949900
hypothetical protein


PA3742
9949910
50S ribosomal protein L19
rplS


PA3743
9949911
tRNA (guanine-N1)-methyltransferase
trmD


PA3744
9949912
16S rRNA processing protein
rimM


PA3745
9949913
30S ribosomal protein S16
rpsP


PA3746
9949914
signal recognition particle protein Ffh
ffh


PA3752
9949921
hypothetical protein


PA3754
9949923
hypothetical protein

yeaB


PA3756
9949925
hypothetical protein

yafK


PA3759
9949928
probable aminotransferase


PA3765
9949935
hypothetical protein


PA3767
9949937
conserved hypothetical protein

yfhC


PA3769
9949940
GMP synthase
guaA


PA3773
9949944
hypothetical protein


PA3776
9949947
probable transcriptional regulator


PA3777
9949948
exodeoxyribonuclease VII large subunit
xseA


PA3782
9949954
probable transcriptional regulator


PA3784
9949956
hypothetical protein


PA3785
9949957
conserved hypothetical protein


PA3787
9949959
conserved hypothetical protein


PA3788
9949960
hypothetical protein


PA3796
9949969
hypothetical protein


PA3800
9949973
conserved hypothetical protein


PA3803
9949976
conserved hypothetical protein

gcpE


PA3805
9949978
type 4 fimbrial biogenesis protein PilF
pilF


PA3806
9949979
conserved hypothetical protein

yfgB


PA3807
9949980
nucleoside diphosphate kinase
ndk


PA3808
9949982
conserved hypothetical protein

yfhJ


PA3809
9949983
ferredoxin [2Fe-2S]
fdx2


PA3810
9949984
heat shock protein HscA
hscA


PA3811
9949985
heat shock protein HscB
hscB


PA3812
9949986
probable iron-binding protein IscA
iscA


PA3813
9949987
probable iron-binding protein IscU
iscU


PA3815
9949989
conserved hypothetical protein


PA3821
9949995
secretion protein SecD
secD


PA3822
9949996
conserved hypothetical protein

yajC


PA3827
9950002
conserved hypothetical protein

yjgQ


PA3828
9950003
conserved hypothetical protein

yjgP


PA3829
9950004
hypothetical protein


PA3833
9950008
hypothetical protein


PA3834
9950009
valyl-tRNA synthetase
valS


PA3835
9950010
hypothetical protein


PA3840
9950016
conserved hypothetical protein

ybiN


PA3843
9950019
hypothetical protein


PA3850
9950027
hypothetical protein


PA3851
9950028
hypothetical protein


PA3854
9950031
hypothetical protein


PA3856
9950033
hypothetical protein


PA3867
9960034
conserved hypothetical protein


PA3859
9950037
probable carboxylesterase



PA3867
9950046
probable DNA invertase


PA3868
9950047
hypothetical protein


PA3869
9950048
hypothetical protein


PA3876
9950056
nitrite extrusion protein 2
narK2


PA3884
9950064
hypothetical protein


PA3886
9950066
hypothetical protein


PA3888
9950069
probable permease of ABC transporter


PA3890
9950071
probable permease of ABC transporter


PA3891
9950072
probable ATP-binding component of ABC tran


PA3892
9950073
conserved hypothetical protein


PA3904
9950087
hypothetical protein


PA3905
9950088
hypothetical protein


PA3906
9950089
hypothetical protein


PA3911
9950094
conserved hypothetical protein

yhbT


PA3916
9950100
molybdopterin converting factor, large subunit
moaE


PA3917
9950101
molybdopterin converting factor, small subunit
moaD


PA3918
9950102
molybdopterin biosynthetic protein C
moaC


PA3936
9950122
probable permease of ABC taurine transported

tauC


PA3940
9950127
probable DNA binding protein


PA3960
9950149
hypothetical protein


PA3962
9950151
hypothetical protein


PA3965
9950154
probable transcriptional regulator


PA3967
9950156
hypothetical protein


PA3969
9950158
conserved hypothetical protein


PA3973
9950163
probable transcriptional regulator


PA3977
9950167
glutamate-1-semialdehyde 2,1-aminomutase
hemL


PA3979
9950170
hypothetical protein


PA3981
9950172
conserved hypothetical protein

ybeZ


PA3982
9950173
conserved hypothetical protein


PA3984
9950175
apolipoprotein N-acyltransferase
Int
cutE


PA3986
9950177
hypothetical protein


PA3987
9950178
leucyl-tRNA synthetase
leuS


PA3988
9950179
hypothetical protein


PA3989
9950180
DNA polymerase III, delta subunit
holA


PA3990
9950182
conserved hypothetical protein


PA3993
9950185
probable transposase


PA3996
9950188
lipoate synthase
lipA
lip


PA3998
9950190
conserved hypothetical protein

ybeD


PA4002
9950194
rod shape-determining protein
rodA
mrdB


PA4005
9950197
conserved hypothetical protein

ybeB


PA4005
9950198
hypothetical protein

ybeN


PA4008
9950201
probable hydrolase


PA4012
9950205
hypothetical protein


PA4018
9950211
hypothetical protein


PA4019
9950212
probable aromatic acid decarboxylase


PA4028
9950222
hypothetical protein


PA4029
9950224
conserved hypothetical protein

dedA


PA4031
9950226
inorganic pyrophosphatase
ppa
ipyR


PA4033
9950228
hypothetical protein


PA4037
9950232
probable ATP-binding component of ABC trans


PA4043
9950239
geranyltranstransferase
ispA


PA4044
9950240
1-deoxyxylulose-5-phosphate synthase
dxs


PA4047
9950243
GTP cyclohydrolase II
ribA


PA4049
9950245
hypothetical protein


PA4050
9950246
phosphatidylycerophosphatase A
pgpA


PA4051
9950247
thiamine monophosphate kinase
thiL


PA4052
9950248
NusB protein
nusB
ssyB


PA4053
9950249
6,7-dimethyl-8-ribityllumazine synthase
ribE
ribH


PA4055
9950252
riboflavin synthase alpha chain
ribC
ribB


PA4056
9950253
riboflavin-specific deaminase/reductase
ribC
ribG


PA4057
9950254
conserved hypothetical protein

ybaD


PA4059
9950256
hypothetical protein


PA4060
9950257
hypothetical protein


PA4063
9950260
hypothetical protein


PA4064
9950261
probable ATP-binding component of ABC trans


PA4068
9950266
probable epimerase


PA4076
9950274
hypothetical protein


PA4077
9950275
probable transcriptional regulator


PA4083
9950282
probable pili assembly chaperone


PA4097
9950298
probable alcohol dehydrogenase (Zn-dependent)

ydjL


PA4099
9950300
hypothetical protein


PA4104
9950305
conserved hypothetical protein


PA4107
9950309
hypothetical protein


PA4114
9950317
spermidine acetyltransferase

bltD


PA4121
9950324
conserved hypothetical protein


PA4122
9950325
conserved hypothetical protein


PA4125
9950329
5-carboxymethyl-2-hydroxymuconate isomera

hpcD


PA4134
9950339
hypothetical protein


PA4141
9950346
hypothetical protein


PA4149
9950351
conserved hypothetical protein

acoX


PA4151
9950357
acetoin catabolism protein AcoB
acoB


PA4157
9950364
probable transcriptional regulator


PA4164
9950372
hypothetical protein


PA4167
9950375
probable oxidoreductase

yafB


PA4169
9950377
conserved hypothetical protein


PA4170
9950378
hypothetical protein


PA4171
9950379
probable protease


PA4174
9950383
probable transcriptional regulator


PA4176
9950385
peptidyl-prolyl cis-trans isomerase C2
ppiC2


PA4181
9950390
hypothetical protein


PA4182
9950391
hypothetical protein


PA4183
9950392
hypothetical protein


PA4190
9950400
probable FAD-dependent monooxygenase


PA4209
9950421
probable O-methyltransterase


PA4210
9950423
probable phenazine biosynthesis protein

phzA1


PA4211
9950424
probable phenazine biosynthesis protein

phzB1


PA4212
9950425
phenazine biosynthesis protein PhzC

phzC1


PA4215
9950428
probable phenazine biosynthesis protein

phzF1


PA4216
9950430
probable pyridoxamine 5′-phosphate oxidase

phzG1


PA4219
9950433
hypothetical protein

yfpB


PA4230
9950446
salicylate biosynthesis protein PchB
pchB


PA4232
9950448
single-stranded DNA-binding protein
ssb


PA4237
9950454
50S ribosomal protein L17
rplQ


PA4238
9950455
DNA-directed RNA polymerase alpha chain
rpoA


PA4239
9950456
30S ribosomal protein S4
rpsD


PA4240
9950457
30S ribosomal protein S11
rpsK


PA4241
9950458
30S ribosomal protein S13
rpsM


PA4242
9950459
50S ribosomal protein L36
rpmJ


PA4243
9950460
secretion protein SecY
secY
prlA


PA4244
9950461
50S ribosomal protein L15
rplO


PA4245
9950462
50S ribosomal protein L30
rpmD


PA4246
9950463
30S ribosomal protein S5
rpsE


PA4247
9950454
50S ribosomal protein L18
rplR


PA4248
9950465
50S ribosomal protein L6
rplF


PA4249
9950466
30S ribosomal protein S8
rpsH


PA4250
9950467
30S ribosomal protein S14
rpsN


PA4251
9950468
50S ribosomal protein L5
rplE


PA4252
9950469
50S ribosomal protein L24
rplX


PA4253
9950470
50S ribosomal protein L14
rplN


PA4254
9950471
30S ribosomal protein S17
rpsQ


PA4255
9950472
50S ribosomal protein L29
rpmC


PA4256
9950473
50S ribosomal protein L16
rplP


PA4257
9950474
30S ribosomal protein S3
rpsC


PA4258
9950475
50S ribosomal protein L22
rplV


PA4259
9950476
30S ribosomal protein S19
rpsS


PA4260
9950477
50S ribosomal protein L2
rpB


PA4261
9950478
50S ribosomal protein L23
rplW


PA4262
9950479
50S ribosomal protein L4
rplD


PA4263
9950480
50S ribosomal protein L3
rplC


PA4264
9950482
30S ribosomal protein S10
rpsJ


PA4267
9950485
30S ribosomal protein S7
rpsG


PA4268
9950486
30S ribosomal protein S12
rpsL
str


PA4269
9950487
DNA-directed RNA polymerase beta* chain
rpoC


PA4270
9950488
DNA-directed RNA polymerase beta chain
rpoB


PA4271
9950490
50S ribosomal protein L7 / L12
rplL


PA4272
9950491
50S ribosomal protein L10
rplJ


PA4273
9950492
50S ribosomal protein L1
rplA


PA4274
9950493
50S ribosomal protein L11
rplK


PA4275
9950494
transcription antitermination protein NusG
nusG


PA4276
9950495
secretion protein SecE
secE
prlG


PA4279
9950498
hypothetical protein


PA4295
9950516
hypothetical protein


PA4296
9950518
probable two-component response regulator


PA4298
9950520
hypothetical protein


PA4299
9950521
hypothetical protein


PA4305
9950527
hypothetical protein


PA4306
9950529
hypothetical protein


PA4314
9950538
formyltetrahydrofolate deformylase
purU1


PA4322
9950546
conserved hypothetical protein


PA4324
9950548
hypothetical protein


PA4329
9950554
pyruvate kinase II
pykA
pyk-II


PA4330
9950555
probable enoyl-CoA hydratase/isomerase


PA4341
9950567
probable transcriptional regulator


PA4345
9950572
hypothetical protein


PA4348
9950575
conserved hypothetical protein


PA4349
9950576
hypothetical protein


PA4350
9950577
conserved hypothetical protein


PA4354
9950581
conserved hypothetical protein


PA4357
9950584
conserved hypothetical protein

yhgG


PA4359
9950585
conserved hypothetical protein

feoA


PA4366
9950594
superoxide dismutase
sodB


PA4373
9960602
hypothetical protein


PA4377
9960607
hypothetical protein


PA4383
9950613
conserved hypothetical protein

crcB


PA4385
9950615
GroEL protein
groEL
mopA


PA4386
9950616
GroES protein
groES
mopB


PA4388
9950618
hypothetical protein


PA4389
9950619
probable short-chain dehydrogenase


PA4392
9950623
conserved hypothetical protein

ybaZ


PA4395
9950626
conserved hypothetical protein

yajQ


PA4403
9950635
secretion protein SecA
secA


PA4405
9950637
hypothetical protein


PA4406
9950638
UDP-3-O-acyl-N-acetylglucosamine deacetyla
lpxC
envA asmB


PA4407
9950639
cell division protein FtsZ
ftsZ


PA4408
9950640
cell division protein FtsA
ftsA


PA4409
9950641
cell division protein FtsQ
ftsQ


PA4411
9950643
UDP-N-acetylmuramate--alanine ligase
murC


PA4412
9950644
UDP N acetylglucosarnine--N-acetylmuramyl
murG


PA4413
9950645
cell division protein FtsW
ftsW


PA4414
9950646
UDP-N-acetylnluramoylalanine--D-glutamate
murD


PA4415
9950647
phospho-N-acetylmuramoyl-pentapeptide-tran
mraY
ORF Y


PA4416
9950648
UDP-N-acetylmuramoylalanyl-D-glutamyl-2, 6-
murF


PA4417
9950649
UDP-N-acetylmuramoylalanyl-D-glutamate-2, 6
murE


PA4418
9950650
penicillin-binding protein 3
ftsl
pbpB


PA4419
9950651
cell division protein FtsL
ftsL


PA4420
9950652
conserved hypothetical protein

mraW yabC ylxA


PA4421
9950653
conserved hypothetical protein

yabB


PA4424
9950657
conserved hypothetical protein

yraN


PA4425
9950658
probable phosphoheptose isomerase

yraO


PA4427
9950660
stringent starvation protein B
sspB


PA4428
9950661
stringent starvation protein A
sspA
ssp pog


PA4430
9950663
probable cytochrome b


PA4432
9950665
30S ribosomal protein S9
rpsl


PA4433
9950666
50S ribosomal protein L13
rplM


PA4436
9950670
probable transcriptional regulator


PA4438
9950672
conserved hypothetical protein

yhcM


PA4439
9950673
tryptophanyl-tRNA synthetase
trpS


PA4440
9950674
hypothetical protein


PA4450
9950685
UDP-N-acetylglucosamine 1-carboxyvinyltrans
murA


PA4452
9950687
conserved hypothetical protein


PA4453
9950688
conserved hypothetical protein


PA4454
9950689
conserved hypothetical protein

yrbD


PA4455
9950690
probable permease of ABC transporter

yrbE


PA4457
9950693
conserved hypothetical protein

yrbH kpsF


PA4459
9950695
conserved hypothetical protein

yrbK


PA4460
9950696
conserved hypothetical protein

yhbN


PA4461
9950697
probable ATP-binding component of ABC trans

yhbG


PA4462
9950698
RNA polymerase sigrna-54 factor
rpoN
ntrA


PA4463
9950699
conserved hypothetical protein

yhbH


PA4464
9950700
nitrogen regulatory IIA protein
ptsN


PA4466
9950702
probable phosphoryl carrier protein


PA4471
9950707
hypothetical protein

fagA


PA4480
9950718
rod shape-determining protein MreC
mreC


PA4481
9950719
rod shape-determining protein MreB
mreB
envB rodY


PA4482
9950720
Glu-tRNA(Gln) amidotransferase subunit C
gatC


PA4483
9950721
Glu-tRNA(Gln) amidotransferase subunit A
gatA


PA4484
9950722
Glu-tRNA(Gln) amidotransferase subunit B
gatB


PA4485
9950723
conserved hypothetical protein


PA4492
9950730
conserved hypothetical protein


PA4499
9950738
probable transcriptional regulator


PA4507
9950747
hypothetical protein


PA4524
9950766
nicotinate-nucleotide pyrophosphorylase
nadC


PA4525
9950767
type 4 fimbrial precursor PilA
pilA


PA4526
9950768
type 4 fimbrial biogenesis protein PilB
pilB


PA4527
9950770
still frameshift type 4 fimbrial biogenesis prote
pilC


PA4529
9950772
conserved hypothetical protein


PA4530
9950773
conserved hypothetical protein


PA4537
9950780
hypothetical protein


PA4544
9950788
pseudouridine synthase
rluD
yfil


PA4547
9950791
two-component response regulator PilR
pilR


PA4552
9950797
type 4 fimbrial biogenesis protein PiIW
pilW


PA4553
9950798
type 4 fimbrial biogenesis protein PiIX
pilX


PA4557
9950802
LytB protein
lytB


PA4559
9950804
prolipoprotein signal peptidase
lspA


PA4560
9950805
isoleucyl-tRNA synthetase
ileS


PA4561
9950806
riboflavin kinase/FAD synthase
ribF


PA4563
9950809
30S ribosomal protein S20
rpsT


PA4564
9950810
conserved hypothetical protein

creA


PA4565
9950811
glutamate 5-kinase
proB


PA4566
9950812
GTP-binding protein Obg
obg


PA4567
9950813
50S ribosomal protein L27
rpmA


PA4558
9950814
50S ribosomal protein L21
rplU


PA4569
9950815
octaprenyl-diphosphate synthase
ispB
cel


PA4674
9950821
conserved hypothetical protein

yqhA


PA4575
9950822
hypothetical protein


PA4577
9950824
hypothetical protein


PA4586
9950834
hypothetical protein


PA4600
9950850
transcriptional regulator NfxB
nfxB


PA4603
9950853
hypothetical protein


PA4610
9950861
hypothetical protein


PA4611
9950862
hypothetical protein


PA4617
9950868
conserved hypothetical protein

yqjO


PA4630
9950883
hypothetical protein


PA4636
9950890
hypothetical protein


PA4637
9950891
hypothetical protein


PA4638
9950892
hypothetical protein


PA4642
9950895
hypothetical protein


PA4644
9950897
hypothetical protein


PA4646
9950899
uracil phosphoribosyltransferase
upp


PA4649
9950903
hypothetical protein


PA4651
9950905
probable pili assembly chaperone


PA4655
9950909
ferrochelatase
hemH
visA


PA4662
9950917
glutamate racemase
murl


PA4663
9950918
molybdopterin biosynthesis MoeB protein
moeB
chlN


PA4665
9950920
peptide chain release factor 1
prfA
rf1


PA4666
9950921
glutamyl-tRNA reductase
hemA
hem1; glutR


PA4668
9950923
probable lipoprotein localization protein LolB

lolB


PA4669
9950924
isopentenyl monophosphate kinase
ipk
ychB


PA4670
9950925
ribose-phosphate pyrophosphokinase
prs
prsA


PA4671
9950927
probable ribosomal protein L25

rplY


PA4672
9950928
peptidyl-tRNA hydrolase

pth


PA4674
9950930
conserved hypothetical protein

vapl


PA4676
9950932
probable carbonic anhydrase

yadF


PA4679
9950935
hypothetical protein


PA4681
9950937
hypothetical protein


PA4693
9950950
phosphatidylserine synthase
pssA


PA4696
9950953
acetolactate synthase large subunit
ilvl


PA4697
9950955
hypothetical protein


PA4698
9950956
hypothetical protein

yqcC


PA4699
9950957
hypothetical protein


PA4702
9950960
hypothetical protein


PA4706
9950964
probable ATP-binding component of ABC trans

phuV


PA4711
9950970
hypothetical protein


PA4718
9950977
hypothetical protein


PA4728
9950988
2-amino-4-hydroxy-6-hydroxymethyldihydropte
folK


PA4729
9950989
3-methyl-2-oxobutanoate hydroxymethyltransfe
panB


PA4731
9950992
aspartate 1-decarboxylase precursor
panD


PA4732
9950993
glucose-6-phosphate isomerase
pgi


PA4737
9950998
hypothetical protein


PA4738
9950999
conserved hypothetical protein

yjbJ


PA4739
9951000
conserved hypothetical protein


PA4740
9951002
polyribonucleotide nucleotidyltransferase
pnp


PA4741
9951003
30S ribosomal protein S15
rpsO


PA4744
9951006
translation initiation factor IF-2
infB


PA4745
9951007
N utilization substance protein A
nusA


PA4746
9951008
conserved hypothetical protein

yhbC


PA4747
9951009
secretion protein SecG
secG


PA4748
9951010
triosephosphate isomerase
tpiA
tpi


PA4749
9951011
phosphoglucosaminemutase
glmM
yhbF, mrsA


PA4750
9951012
dihydropteroate synthase
folP
dhpS


PA4752
9951015
cell division protein FtsJ
ftsJ


PA4753
9951016
conserved hypothetical protein

yhbY


PA4757
9951020
conserved hypothetical protein

yeaS


PA4759
9951022
dihydrodipicolinate reductase
dapB


PA4762
9951028
heat shock protein GrpE
gpE


PA4764
9951028
ferric uptake regulation protein
fur


PA4765
9951029
outer membrane lipoprotein OmlA
omlA
oprX


PA4767
9951031
conserved hypothetical protein

yfjG


PA4773
9951038
hypothetical protein


PA4776
9951041
probable two-component response regulator


PA4778
9951043
probable transcriptional regulator

ybbl


PA4782
9951047
hypothetical protein


PA4788
9951054
hypothetical protein


PA4789
9951055
conserved hypothetical protein


PA4790
9951056
conserved hypothetical protein

smtA


PA4792
9951058
conserved hypothetical protein


PA4797
9951064
probable transposase


PA4802
9951069
hypothetical protein


PA4809
9951077
FdhE protein
fdhE


PA4813
9951080
lipase LipC
lipC


PA4823
9951091
hypothetical protein


PA4826
9951095
hypothetical protein


PA4828
9951097
conserved hypothtial protein


PA4831
9951100
probable transcriptional regulator


PA4841
9951111
conserved hypothetical protein


PA4484
9951118
biotin carboxyl carrier protein (BCCP)
accB
fabE


PA4848
9951119
biotin carboxylase
accC


PA4850
9951121
ribosomal protein L11 methyltransferase
prmA


PA4853
9951124
DNA-binding protein Fis
fis


PA4861
9951133
probable ATP-binding component of ABC trans


PA4864
9951137
urease accessory protein
ureD


PA4866
9951139
conserved hypothetical protein


PA4868
9951141
urease alpha subunit
ureC


PA4870
9951143
conserved hypothetical protein

ybil


PA4871
9951144
hypothetical protein


PA4874
9951148
conserved hypothetical protein

psiF


PA4875
9951149
hypothetical protein


PA4878
9951152
probable transcriptional regulator


PA4885
9951159
two-component response regulator
irlR


PA4887
9951161
probable MFS transporter


PA4890
9951165
conserved hypothetical protein

yijC


PA4892
9951167
urease accessory protein UreF
ureF


PA4894
9951169
hypothetical protein


PA4895
9951170
probable transmembrane sensor


PA4906
9951182
probable transcriptional regulator


PA4908
9951185
hypothetical protein


PA4916
9951193
hypothetical protein


PA4920
9951198
NH3-dependent NAD synthetase
nadE


PA4923
9951201
conserved hypothetical protein


PA4925
9951203
conserved hypothetical protein


PA4926
995l204
conserved hypothetical protein


PA4931
9951210
replicative DNA helicase
dnaB


PA4934
9951213
30S ribosomal protein S18
rpsR


PA4935
9951214
30S ribosomal protein S6
rpsF


PA4938
9951218
adenylosuccinate synthetase
purA


PA4940
9951220
conserved hypothetical protein

yjeT


PA4944
9951224
conserved hypothetical protein

hfq


PA4945
9951225
delta 2-isopentenylpyrophosphate transferase
miaA


PA4948
9951228
conserved hypothetical protein

yjeE


PA4952
9951233
conserved hypothetical protein

yjeQ


PA4956
9951237
thiosulfate sulfurtransferase
rhdA


PA4951
9951243
hypothetical protein


PA4962
9951244
conserved hypothetical protein

ybcl


PA4964
9951246
topoisomerase IV subunit A
parC


PA4965
9951247
hypothetical protein


PA4966
9951248
hypothetical protein


PA4967
9951249
topoisomerase IV subunit B
parE


PA4969
9951252
conserved hypothetical protein

icc


PA4972
9951255
hypothetical protein


PA4980
9951263
probable enoyl-CoA hydratase/isomerase


PA4988
9951272
3-deoxy-D-manno-octulosonic-acid (KDO) tran
waaA
kdtA


PA4990
9951275
SMR multidrug efflux transporter


PA4991
9951276
hypothetical protein


PA4992
9951277
hypothetical protein


PA4997
9951282
transport protein MsbA
msbA


PA4998
9951283
conserved hypothetical protein


PA5006
9951292
hypothetical protein


PA5007
9951293
hypothetical protein

wapQ inaA


PA5008
9951294
hypothetical protein

wapP waaX


PA5009
9951295
lipopolysaccharide core biosynthesis protein W
waaP
rfaP


PA5010
9951296
UDP-glucose:(heptosyl) LPS alpha 1,3-glucosy
waaG
rfaG


PA5011
9951297
heptosyltransferase I
waaC
rfaC


PA5012
9951298
heptosyltransferase II
waaF
rfaF


PA5028
9951317
conserved hypothetical protein


PA5032
9951321
probable transcriptional regulator


PA5033
9951322
hypothetical protein


PA5034
9951323
uroporphyrinogen decarboxylase
hemE


PA5039
9951329
shikimate kinase
aroK


PA5044
9951334
type 4 fimbrial biogenesis protein PilM
pilM


PA5050
9951341
primosomal protein N′
priA


PA5051
9951342
arginyl-tRNA synthetase
argS


PA5052
9951343
hypothetical protein


PA5061
9951353
conserved hypothetical protein

phal


PA5063
9951355
ubiquinone biosynthesis methyltransferase Ub
ubiE


PA5064
9951356
hypothetical protein


PA5065
9951357
conserved hypothetical protein

aarF yigR


PA5067
995l360
phosphoribosyl-ATP pyrophosphohydrolase
hisE


PA5068
9951361
translocation protein TatA
tatA
mttA yigT


PA5071
9951364
conserved hypothetical protein


PA5072
9951365
probable chemotaxis transducer


PA5081
9951375
hypothetical protein


PA5085
9951379
probable transcriptional regulator


PA5110
9951406
fructose-1,6-bisphosphatase
fbp
cbbF, cfxF


PA5111
9951408
lactoylglutathione lyase
gloA3
glo1


PA5116
9951413
probable transcriptional regulator


PA5119
9951417
glutamine synthetase
glnA


PA5128
9951427
secretion protein SecB
secB


PA5129
9951428
glutaredoxin
grx


PA5130
9951429
conserved hypothetical protein

yibN


PA5131
9951430
phosphoglycerate mutase
pgm
yibO


PA5132
9951431
hypothetical protein


PA5142
9951442
glutamine amidotransferase
hisH1


PA5144
9951444
hypothetical protein


PA5148
9951448
conserved hypothetical protein

yggX


PA5154
9951455
probable permease of ABC transporter


PA5161
9951463
dTDP-D-glucose 4,6-dehydratase
rmlB
rfbB


PA5162
9951464
dTDP-4-dehydrorhamnose reductase
rmlD
rfbD


PA5163
9951465
glucose-1-phosphate thymidylyltransferase
rmlA
rfbA


PA5164
9951466
dTDP-4-dehydrorhamnose 3,5-epimerase
rmlC
rfbC


PA5173
9951476
carbamate kinase
arcC


PA5176
9951479
conserved hypothetical protein

yrfE


PA5178
9951481
conserved hypothetical protein


PA5182
9951486
hypothetical protein


PA5187
9951491
probable acyl-CoA dehydrogenase


PA5190
9951495
probable nitroreductase


PA5195
9951500
probable heat shock protein

yrfH


PA5221
9951529
probable FAD-dependent monooxygenase

visC


PA5222
9951530
hypothetical protein


PA5224
9951532
aminopeptidase P
pepP


PA5225
9951533
hypothetical protein


PA5227
9951535
conserved hypothetical protein

ygfE


PA5229
9951537
conserved hypothetical protein


PA5237
9951546
conserved hypothetical protein

yigC


PA5239
9951548
transcription termination factor Rho
rho


PA5240
9951549
thioredoxin
trxA


PA5246
9951556
conserved hypothetical protein

yigl


PA5247
9951557
conserved hypothetical protein

yail


PA5259
9951570
uroporphyrinogen-III synthetase
hemD


PA5260
9951571
porphobilinogen deaminase
hemC
popE


PA5275
9951588
conserved hypothetical protein

cyaY


PA5276
9951589
lipopeptide LppL precursor
lppL


PA5278
9951591
diaminopimelate epimerase
dapF


PA5281
9951594
probable hydrolase

yigB


PA5288
9951602
nitrogen regulatory protein P-II 2
glnK


PA5296
9951611
ATP-dependent DNA helicase Rep
rep


PA5300
9951616
cytochnome c5
cycB


PA5303
9951619
conserved hypothetical protein


PA5316
9951633
50S ribosomal protein L28
rpmB


PA5319
9951636
DNA repair protein RadC
radC


PA5320
9951637
DNA/pantothenate metabolism flavoprotein
dfp


PA5321
9951638
deoxyuridine 5′-triphosphate nucleotidohydrola
dut


PA5325
9951643
hypothetical protein


PA5327
9951646
probable cytochrome c(mono-heme type)


PA5330
9951648
hypothetical protein


PA5331
9961649
orotate phosphoribosyltransferase
pyrE


PA5333
9951652
conserved hypothetical protein


PA5334
9951653
ribonuclease PH
rph


PA5335
9951654
conserveci hypothetical protein

yicC


PA5336
9951655
guanylate kinase
gmk


PA5339
9951658
conserved hypothetical protein


PA5347
9951667
hypothetical protein


PA5350
9951670
rubredoxin


PA5351
9951671
rubredoxin


PA5358
9951678
4-hydroxybenzoate-octaprenyl transferase
ubiA


PA5364
9951685
probable two-component response regulator


PA5381
9951704
hypothetical protein


PA5385
9951709
hypothetical protein


PA5390
9951714
probable peptidic bond hydrolase


PA5396
9951721
hypothetical protein


PA5403
9951729
probable transcriptional regulator


PA5404
9951730
hypothetical protein


PA5406
9951732
hypothetical protein


PA5408
9951734
hypothetical protein


PA5417
9951744
sarcosine oxidase delta subunit
soxD


PA5457
9951788
hypothetical protein


PA5460
9951792
hypothetical protein


PA5465
9951797
hypothetical protein


PA5469
9951801
conserved hypothetical protein


PA5470
9951802
probable peptide chain release factor

prfH


PA5480
9951813
hypothetical protein


PA5482
9951816
hypothetical protein


PA5496
9951831
hypothetical protein


PA5503
9951839
probable ATP-binding component of ABC trans


PA5526
9951864
hypothetical protein


PA5529
9951867
probable sodium/proton antiporter


PA5531
9951869
TonB protein
tonB


PA5533
9951871
hypothetical protein


PA5534
9951873
hypothetical protein


PA5543
9951882
hypothetical protein


PA5549
9951889
glucosamine--fructose-6-phosphate aminotran
glmS


PA5552
9951692
glucosamine-1-phosphate acetyltransferase/N
glmU
gcaD


PA5553
9951893
ATP synthase epsilon chain
atpC
uncC papG


PA5554
9951894
ATP synthase beta chain
atpD
uncD papB


PA5555
9951895
ATP synthase gamma chain
atpG
uncG papC


PA5556
9951896
ATP synthase alpha chain
atpA
uncA papA


PA5557
9951897
ATP synthase delta chain
atpH
uncH papE


PA5558
9951898
ATP synthase B chain
atpF
uncF papF


PA5559
9951899
atp synthase C chain
atpE
uncE papH


PA5560
9951900
ATP synthase A chain
atpB
unoB papD


PA5561
9951901
ATP synthase protein I
atpl
uncl


PA5562
9951903
chromosome partitioning protein SpoOJ
spoOJ


PA5566
9951907
hypothetical protein


PA5568
9951909
conserved hypothetical protein

yidC


PA5569
9951910
ribonuclease P protein component
rnpA


PA5570
9951911
50S ribosomal protein L34
rpmH












Primary Function
Range From
Range To





DNA replication, recombination, modification
483
2027


DNA replication, recombination, modification
4275
6695


Hypothetical, unclassified, unknown
8339
7803


Translation, post-translational modification
12488
10434


Translation, post-translational modification
13435
12488


Cell wall / LPS / capsule
14235
15122


Hypothetical, unclassified, unknown
17217
16900


Hypothetical, unclassified, unknown
24001
24558


Hypothetical, unclassified, unknown
27646
28632


Hypothetical, unclassified, unknown
36270
35905


Amino acid biosynthesis and metabolism
37893
37087


Hypothetical, unclassified, unknown
40190
40405


Hypothetical, unclassified, unknown
40589
40816


Hypothetical, unclassified, unknown
56546
56941


Hypothetical, unclassified, unknown
61879
62388


Hypothetical, unclassified, unknown
68618
68188


Hypothetical, unclassified, unknown
69272
69526


Hypothetical, unclassified, unknown
70091
69543


Hypothetical, unclassified, unknown
70636
70130


Hypothetical, unclassified, unknown
72680
73384


Adaptation, protection
73468
73923


Hypothetical, unclassified, unknown
74034
74267


Hypothetical, unclassified, unknown
74716
74279


Hypothetical, unclassified, unknown
78097
77432


Hypothetical, unclassified, unknown
80752
81027


Hypothetical, unclassified, unknown
81116
82174


Hypothetical, unclassified, unknown
83318
82404


Hypothetical, unclassified, unknown
98218
97754


Hypothetical, unclassified, unknown
100124
101158


Hypothetical, unclassified, unknown
115045
114611


Hypothetical, unclassified, unknown
119127
120164


Hypothetical, unclassified, unknown
121346
122266


Energy metabolism
127378
128502


Hypothetical, unclassified, unknown
131792
131583


Hypothetical, unclassified, unknown
132577
133155


Energy metabolism
134319
135233


Hypothetical, unclassified, unknown
135259
135894


Hypothetical, unclassified, unknown
136386
135934


Hypothetical, unclassified, unknown
136518
136991


Transport of small molecules
138818
140167


Transcriptional regulators
140216
140902


Hypothetical, unclassified, unknown
143848
143567


Hypothetical, unclassified, unknown
144072
143845


Hypothetical, unclassified, unknown
145542
145883


Hypothetical, unclassified, unknown
149425
149138


Transcriptional regulators
150906
151823


Hypothetical, unclassified, unknown
153696
153836


Adaptation, protection
158199
158762


Nucleotide biosynthesis and metabolism
163426
184415


Hypothetical, unclassified, unknown
165737
165219


Transcriptional regulators
169361
169906


Carbon compound catabolism
175503
176108


Transcriptional regulators
182768
183706


Hypothetical, unclassified, unknown
184287
184439


Transcriptional regulators
191697
192362


Hypothetical, unclassified, unknown
194179
193799


Hypothetical, unclassified, unknown
194748
194206


Putative enzymes
207071
207823


Carbon compound catabolism
209533
207923


Transport of small molecules
210460
209621


Hypothetical, unclassified, unknown
213819
214634


Hypothetical, unclassified, unknown
214631
215512


Hypothetical, unclassified, unknown
229738
229526


Putative enzymes
232000
230543


Transport of small molecules
233100
232066


Transport of small molecules
233932
233123


Transport of small molecules
234849
233929


Transcriptional regulators
236218
237111


Hypothetical, unclassified, unknown
238896
239777


Carbon compound catabolism
240071
240934


Hypothetical, unclassified, unknown
241753
242445


Transport of small molecules
243841
244605


Transcriptional regulators
262557
263498


Transcriptional regulators
266616
267395


Hypothetical, unclassified, unknown
268704
269519


Transcriptional regulators
275772
276440


Hypothetical, unclassified, unknown
277334
276480


Amino acid biosynthesis and metabolism
277777
277331


Hypothetical, unclassified, unknown
282767
282323


Hypothetical, unclassified, unknown
283553
282912


Hypothetical, unclassified, unknown
289390
289205


Hypothetical, unclassified, unknown
293304
291154


Hypothetical, unclassified, unknown
293798
293301


Hypothetical, unclassified, unknown
299497
299081


Transport of small molecules
309092
307878


Transcriptional regulators
313227
313925


Transport of small molecules
314927
313938


Hypothetical, unclassified, unknown
318148
317966


Hypothetical, unclassified, unknown
350841
350089


Hypothetical, unclassified, unknown
352164
351610


Hypothetical, unclassified, unknown
359982
360332


Energy metabolism
371833
371162


Hypothetical, unclassified, unknown
373725
374192


Hypothetical, unclassified, unknown
378096
378575


Hypothetical, unclassified, unknown
382792
382037


Fatty acid and phospholipid metabolism
383727
384527


Nucleotide biosynthesis and metabolism
384733
385527


Biosynthesis of cofactors, prosthetic group
393308
393814


Hypothetical, unclassified, unknown
402020
402598


Energy metabolism
406498
406247


Central intermediary metabolism
407098
406619


Hypothetical, unclassified, unknown
413654
413364


Hypothetical, unclassified, unknown
414529
413933


Protein secretion/export apparatus
417527
418894


Transcriptional regulators
420683
421537


Hypothetical, unclassified, unknown
421602
422207


Hypothetical, unclassified, unknown
423460
423660


Hypothetical, unclassified, unknown
427120
426863


Hypothetical, unclassified, unknown
439991
440395


Nucleotide biosynthesis and metabolism
445691
444687


Transcriptional regulators
446227
445715


Hypothetical, unclassified, unknown
446773
446339


Hypothetical, unclassified, unknown
447342
446773


Biosynthesis of cofactors, prosthetic group
449384
448431


Motility & Attachment
453239
454114


Transcriptional regulators
463079
463873


Hypothetical, unclassified, unknown
470081
470650


Transport of small molecules
476333
477790


Hypothetical, unclassified, unknown
484404
484838


Hypothetical, unclassified, unknown
496478
496362


Transport of small molecules
496871
498361


Related to phage, transposon, or plasmid
501120
500104


Hypothetical, unclassified, unknown
502599
501376


Transcriptional regulators
504121
505029


Hypothetical, unclassified, unknown
510499
509825


Adaptation, protection
514775
514984


Hypothetical, unclassified, unknown
526877
527179


Hypothetical, unclassified, unknown
535085
535489


Transcriptional regulators
535539
536108


Transcriptional regulators
539143
538217


Transcriptional regulators
540735
539785


Hypothetical, unclassified, unknown
549614
549294


Putative enzymes
550381
549656


Hypothetical, unclassified, unknown
550813
550520


Putative enzymes
552746
552994


Hypothetical, unclassified, unknown
558361
557354


Biosynthesis of cofactors, prosthetic group
560808
562013


Biosynthesis of cofactors, prosthetic group
562006
562728


Biosynthesis of cofactors, prosthetic group
562721
563545


Biosynthesis of cofactors, prosthetic group
563549
564235


Hypothetical, unclassified, unknown
564344
564574


Biosynthesis of cofactors, prosthetic group
576040
575516


Transcriptional regulators
586663
585980


Putative enzymes
590105
590821


Transcriptional regulators
594580
595134


Hypothetical, unclassified, unknown
598608
598994


Hypothetical, unclassified, unknown
600176
599757


Hypothetical, unclassified, unknown
600426
601394


Hypothetical, unclassified, unknown
602141
601398


Central intermediary metabolism
604896
603706


Hypothetical, unclassified, unknown
609999
609202


Energy metabolism
611281
612444


Hypothetical, unclassified, unknown
612517
612717


Carbon compound catabolism
613338
614402


Hypothetical, unclassified, unknown
617549
616371


Hypothetical, unclassified, unknown
620438
620135


Hypothetical, unclassified, unknown
621695
622033


Hypothetical, unclassified, unknown
622726
622884


Hypothetical, unclassified, unknown
624199
623852


Hypothetical, unclassified, unknown
624803
624189


Hypothetical, unclassified, unknown
629884
628763


Hypothetical, unclassified, unknown
638830
638381


Translation, post-translational modification
639115
638900


Translation, post-translational modification
639316
640341


Biosynthesis of cofactors, prosthetic group
641073
641426


Hypothetical, unclassified, unknown
643714
643208


Hypothetical, unclassified, unknown
649263
648931


Hypothetical, unclassified, unknown
650538
650158


Biosynthesis of cofactors, prosthetic group
652483
651497


Chaperones & heat shock proteins
653772
652480


Adaptation, protection
656527
653753


Energy metabolism
669415
670089


Transcriptional regulators
673091
672777


Transcriptional regulators
673961
673191


Hypothetical, unclassified, unknown
67466
675026


Hypothetical, unclassified, unknown
675390
675839


Related to phage, transposon, or plasmid
677083
677409


Hypothetical, unclassified, unknown
685846
686718


Hypothetical, unclassified, unknown
686693
686899


Related to phage, transposon, or plasmid
688605
688967


Related to phage, transposon, or plasmid
689236
689466


Related to phage, transposon, or plasmid
690420
690674


Hypothetical, unclassified, unknown
693596
694366


Hypothetical, unclassified, unknown
698932
699720


Hypothetical, unclassified, unknown
699744
700835


Related to phage, transposon, or plasmid
700835
701170


Hypothetical, unclassified, unknown
701477
702529


Related to phage, transposon, or plasmid
702529
702831


Related to phage, transposon, or plasmid
702828
703058


Transportation regulators
706672
706028


Hypothetical, unclassified, unknown
706944
707366


Hypothetical, unclassified, unknown
709182
708535


Hypothetical, unclassified, unknown
714247
713279


Hypothetical, unclassified, unknown
714686
714264


Hypothetical, unclassified, unknown
717231
717581


Protein secretion/export apparatus
737530
737081


Hypothetical, unclassified, unknown
737677
738108


Protein secretion/export apparatus
738485
738111


Protein secretion/export apparatus
741335
741928


Protein secretion/export apparatus
744333
745742


Protein secretion/export apparatus
745742
746956


Hypothetical, unclassified, unknown
748662
749774


Hypothetical, unclassified, unknown
770156
770818


Hypothetical, unclassified, unknown
770847
771326


Hypothetical, unclassified, unknown
772275
772700


Hypothetical, unclassified, unknown
775321
774416


Putative enzymes
778181
776787


Putative enzymes
779208
778309


Transcriptional regulators
782113
781259


Hypothetical, unclassified, unknown
782229
782525


Central intermediary metabolism
782570
782965


Hypothetical, unclassified, unknown
783833
783576


Hypothetical, unclassified, unknown
784698
785174


Hypothetical, unclassified, unknown
785698
786925


Hypothetical, unclassified, unknown
786928
788253


Related to phage, transposon, or plasmid
789144
789356


Related to phage, transposon, or plasmid
790166
790600


Related to phage, transposon, or plasmid
795793
796776


Hypothetical, unclassified, unknown
797251
797598


Putative enzymes
798827
797925


Transcription, RNA processing and degr
801967
801275


Hypothetical, unclassified, unknown
802239
801967


Hypothetical, unclassified, unknown
805228
805473


Hypothetical, unclassified, unknown
809882
809574


Hypothetical, unclassified, unknown
828344
827400


Secreted Factors (toxins, enzymes, algina
831914
832498


Protein secretion/export apparatus
835523
837322


Protein secretion/export apparatus
837328
838182


Translation, post-translational modification
839407
840324


Hypothetical, unclassified, unknown
844295
843723


Hypothetical, unclassified, unknown
845682
845278


Transport of small molecules
858646
858951


Hypothetical, unclassified, unknown
859007
860170


Hypothetical, unclassified, unknown
866451
865636


Hypothetical, unclassified, unknown
881077
881400


Hypothetical, unclassified, unknown
883216
882989


Hypothetical, unclassified, unknown
885635
886108


Transcriptional regulators
893041
893994


Hypothetical, unclassified, unknown
895668
895396


Hypothetical, unclassified, unknown
896416
897228


Hypothetical, unclassified, unknown
898886
898440


Hypothetical, unclassified, unknown
900165
899830


Hypothetical, unclassified, unknown
901046
900408


Putative enzymes
903692
904633


Chaperones & heat shock proteins
913086
913571


Hypothetical, unclassified, unknown
929084
929503


Hypothetical, unclassified, unknown
930476
929514


Put active enzymes
932725
932102


Cell division
935989
936294


Hypothetical, unclassified, unknown
942648
943430


Hypothetical, unclassified, unknown
948776
949159


Hypothetical, unclassified, unknown
949280
949693


Cell wall / LPS / capsule
950648
949716


Amino acid biosynthesis and metabolism
952514
952158


Hypothetical, unclassified, unknown
955722
955456


Putative enzymes
962545
962925


Hypothetical, unclassified, unknown
977743
977420


Hypothetical, unclassified, unknown
984245
984535


Translation, post-translational modification
986818
989442


Amino acid biosynthesis and metabolism
989590
990828


Transcriptional regulators
991013
991198


Transcriptional regulators
992543
991830


Hypothetical, unclassified unknown
993409
993783


Hypothetical, unclassified, unknown
993776
994051


Transport of small molecules
996038
997486


Hypothetical, unclassified, unknown
1007548
1007234


Carbon compound catabolism
1012972
1011983


Amino acid biosynthesis and metabolism
1020708
1021607


Hypothetical, unclassified, unknown
1027445
1027934


Hypothetical, unclassified, unknown
1030151
1029825


Nucleotide biosynthesis and metabolism
1032763
1032095


Nucleotide biosynthesis and metabolism
1033824
1032763


Hypothetical, unclassified, unknown
1035277
1035981


Putative enzymes
1039968
1040432


Putative enzymes
1040432
1040707


Translation, post-translational modification
1043404
1041689


Hypothetical, unclassified, unknown
1046462
1046671


Adaptation, protection
1048019
1047549


Transport of small molecules
1053848
1054543


Transport of small molecules
1054566
1055006


Transport of small molecules
1055009
1056052


Transport of small molecules
1056049
1057347


Transport of small molecules
1057400
1057906


Hypothetical, unclassified, unknown
1059622
1060296


Hypothetical, unclassified, unknown
1062034
1061207


Hypothetical, unclassified, unknown
1062369
1062061


Hypothetical, unclassified, unknown
1062601
1062885


Hypothetical, unclassified, unknown
1062921
1063544


Hypothetical, unclassified, unknown
1065138
1065425


Secreted Factors (toxins, enzymes, algin
1067817
1066321


Hypothetical, unclassified, unknown
1068193
1068456


Hypothetical, unclassified, unknown
1071877
1071239


Hypothetical, unclassified, unknown
1072462
1072839


Chaperones & heat shock proteins
1073960
1074673


Hypothetical, unclassified, unknown
1082949
1083854


Hypothetical, unclassified, unknown
1090606
1090857


Adaptation, protection
1092498
1092025


Amino acid biosynthesis and metabolism
1093251
1094129


Hypothetical, unclassified, unknown
1095276
1096034


Nucleotide biosynthesis and metabolism
1096063
1096773


Putative enzymes
1107000
1107761


Hypothetical, unclassified, unknown
1113050
1112574


Hypothetical, unclassified, unknown
1123850
1123356


Hypothetical, unclassified, unknown
1125865
1125548


Hypothetical, unclassified, unknown
1126338
1125865


Biosynthesis of cofactors, prosthetic group
1136388
1137035


Hypothetical, unclassified, unknown
1144862
1145200


Hypothetical, unclassified, unknown
1150470
1150721


Chaperones & heat shock proteins
1153637
1155547


Hypothetical, unclassified, unknown
1163660
1164022


Hypothetical, unclassified, unknown
1175614
1176375


Hypothetical, unclassified, unknown
1176380
1176982


Hypothetical, unclassified, unknown
1176958
1177620


Hypothetical unclassified, unknown
1186606
1186986


Two-component regulatory systems
1189172
1190380


Motility &Attachment
1194207
1195223


Motility & Attachment
1197390
1197833


Hypothetical, unclassified, unknown
1198551
1197838


Hypothetical, unclassified, unknown
1199946
1198750


Hypothetical, unclassified, unknown
1207875
1207540


Hypothetical, unclassified, unknown
1212571
1211888


Hypothetical, unclassified, unknown
1214502
1213195


Translation, post-translational modification
1215284
1215727


Biosynthesis of cofactors, prosthetic group
1218181
1218933


Antibiotic resistance and susceptibility
1221691
1222098


Hypothetical, unclassified, unknown
1226278
1225757


Hypothetical, unclassified, unknown
1227302
1226427


Transcriptional regulators
1229344
1230219


Transcriptional regulators
1236644
1237546


Hypothetical, unclassified, unknown
1243118
1242750


Adaptation, protection
1245665
1245928


Hypothetical, unclassified, unknown
1249552
1249019


Nucleotide biosynthesis and metabolism
1251154
1249907


Nucleotide biosynthesis and metabolism
1254309
1251418


Two-component regulatory systems
1255042
1255752


Adaptation, protection
1257772
1257981


Hypothetical, unclassified, unknown
1258470
1258087


Amino acid biosynthesis and metabolism
1260442
1259291


Hypothetical, unclassified, unknown
1263378
1264190


Hypothetical, unclassified, unknown
1264919
1264191


Hypothetical, unclassified, unknown
1266111
1266782


Hypothetical, unclassified, unknown
1267282
1267602


Energy metabolism
1272796
1272200


Energy metabolism
1273298
1272807


Energy metabolism
1276608
1276117


Energy metabolism
1276784
1276617


Transport of small molecules
1284513
1265823


Hypothetical, unclassified, unknown
1294138
1294809


Hypothetical, unclassified, unknown
1303457
1303864


Hypothetical, unclassified, unknown
1303892
1304449


Hypothetical, unclassified, unknown
1305583
1306056


Hypothetical, unclassified, unknown
1314321
1313362


Hypothetical, unclassified, unknown
1317202
1315916


Hypothetical, unclassified, unknown
1318150
1317404


Amino acid biosynthesis and metabolism
1319514
1318147


Hypothetical, unclassified, unknown
1321000
1320386


Transcriptional regulators
1326939
1326046


Putative enzymes
1327024
1327803


Hypothetical, unclassified, unknown
1330467
1330117


Hypothetical, unclassified, unknown
1331517
1331714


Hypothetical, unclassified, unknown
1334671
1334928


Antibiotic resistance and susceptibility
1339082
1337931


Secreted Factors (toxins, enzymes, algin
1357317
1357712


Transcriptional regulators
1370092
1369418


Transcriptional regulators
1379168
1378500


Hypothetical, unclassified, unknown
1391277
1391861


Transcriptional regulators
1396731
1397180


Hypothetical, unclassified, unknown
1406459
1406752


Hypothetical, unclassified, unknown
1408999
1409274


Transcriptional regulators
1409949
1410476


Putative enzymes
1417500
1417961


Hypothetical, unclassified, unknown
1417965
1418738


Transcriptional regulators
1425754
1425140


Energy metabolism
1432037
1432927


Hypothetical, unclassified, unknown
1435493
1435825


Transcriptional regulators
1441547
1440639


Hypothetical, unclassified, unknown
1444451
1442904


Transport of small molecules
1456723
1455815


Hypothetical, unclassified, unknown
1462696
1463403


Hypothetical, unclassified, unknown
1463586
1463936


Hypothetical, unclassified, unknown
1464111
1464860


Hypothetical, unclassified, unknown
1467320
1466109


Hypothetical, unclassified, unknown
1467901
1467488


Hypothetical, unclassified, unknown
1468510
1468890


Hypothetical, unclassified, unknown
1470978
1470580


Hypothetical, unclassified, unknown
1474391
1474714


Transcriptional regulators
1475464
1476306


Hypothetical, unclassified, unknown
1479791
1479021


Hypothetical, unclassified, unknown
1483123
1483875


Hypothetical, unclassified, unknown
1483898
1485763


Hypothetical, unclassified, unknown
1486967
1486266


Hypothetical, unclassified, unknown
1489095
1486960


Biosynthesis of cofactors, prosthetic group
1491913
1493055


Hypothetical, unclassified, unknown
1494959
1495492


Hypothetical, unclassified, unknown
1495635
1495997


Putative enzymes
1496920
1496087


Hypothetical, unclassified, unknown
1516433
1516687


Two-component regulatory systems
1518914
1519546


Hypothetical, unclassified, unknown
1519627
1519968


Hypothetical, unclassified, unknown
1526657
1526430


Carbon compound catabolism
1533238
1534278


Hypothetical, unclassified, unknown
1552641
1552997


Hypothetical, unclassified, unknown
1553112
1553675


Transcriptional regulators
1559122
1558880


Adaptation, protection
1559254
1559859


Hypothetical, unclassified, unknown
1572023
1572544


Motility & Attachment
1575290
1575559


Motility & Attachment
1583956
1584798


Two-component regulatory systems
1585640
1586014


Chemotaxis
1591286
1592176


Cell division
1592271
1593059


Chemotaxis
1594087
1594566


Hypothetical, unclassified, unknown
1594597
1595004


Hypothetical, unclassified, unknown
1596889
1597305


Hypothetical, unclassified, unknown
1599982
1599428


Transport of small molecules
1602179
1602880


Transport of small molecules
1602877
1603548


Transport of small molecules
1603671
1604429


Hypothetical, unclassified
1604426
1604602


Energy metabolism
1605088
1607061


Energy metabolism
1607065
1607607


Energy metabolism
1607604
1608071


Hypothetical, unclassified, unknown
1615908
1614670


Hypothetical, unclassified, unknown
1617085
1615895


Hypothetical, unclassified, unknown
1619907
1620263


Transport of small molecules
1624715
1623864


Transcriptional regulators
1634492
1633842


Hypothetical, unclassified, unknown
1638639
1638379


Hypothetical, unclassified, unknown
1639794
1638652


Hypothetical, unclassified, unknown
1647046
1646537


Hypothetical, unclassified, unknown
1649555
1648629


Hypothetical, unclassified, unknown
1649928
1650308


Transcriptional regulators
1660727
1661386


Cell division
1665065
1665934


DNA replication, recombination, modification
1666025
1668409


DNA replication, recombination, modification
1669989
1672034


Hypothetical, unclassified, unknown
1672080
1672406


Putative enzymes
1673204
1674352


Hypothetical, unclassified, unknown
1677559
1678407


Hypothetical, unclassified, unknown
1678590
1678261


Transport of small molecules
1678952
1678584


Hypothetical, unclassified, unknown
1684962
1684753


Energy metabolism
1689339
1687924


Energy metabolism
1694045
1693119


Hypothetical, unclassified, unknown
1696467
1697099


Hypothetical, unclassified, unknown
1697188
1697919


Hypothetical, unclassified, unknown
1697916
1698344


Hypothetical, unclassified, unknown
1704522
1704761


Hypothetical, unclassified, unknown
1709765
1709412


Hypothetical, unclassified, unknown
1712698
1712519


Energy metabolism
1720744
1721130


Energy metabolism
1721124
1721492


Energy metabolism
1721496
1723268


Energy metabolism
1723280
1723987


Energy metabolism
1728416
1729852


Energy metabolism
1730181
1731347


Energy metabolism
1731347
1732234


Hypothetical, unclassified, unknown
1734004
1734768


Hypothetical, unclassified, unknown
1735063
1734827


Hypothetical, unclassified, unknown
1735236
1735709


Hypothetical, unclassified, unknown
1735706
1736152


Hypothetical, unclassified, unknown
1736189
1737418


Fatty acid and phospholipid metabolism
1753418
1752903


Hypothetical, unclassified, unknown
1762433
1762870


Transcriptional regulators
1762928
1763752


Putative enzymes
1765345
1766205


Hypothetical, unclassified, unknown
1766285
1766941


Hypothetical, unclassified, unknown
1766956
1767762


Transcriptional regulators
1773682
1774548


Transport of small molecules
1775945
1776034


Transport of small molecules
1779877
1780428


Hypothetical, unclassified, unknown
1784108
1785016


Hypothetical, unclassified, unknown
1786888
1787166


Hypothetical, unclassified, unknown
1790879
1790472


Hypothetical, unclassified, unknown
1805218
1805724


Hypothetical, unclassified, unknown
1814995
1815135


Hypothetical, unclassified, unknown
1816351
1816858


Hypothetical, unclassified, unknown
1824969
1825430


Biosynthesis of cofactors, prosthetic group
1826040
1825495


Hypothetical, unclassified, unknown
1826675
1826118


Hypothetical, unclassified, unknown
1827052
1826732


Amino acid biosynthesis and metabolism
1836367
1837227


Protein secretion/export apparatus
1841517
1840468


Protein secretion/export apparatus
1842302
1841514


Protein secretion/export apparatus
1845717
1845241


Protein secretion/export apparatus
1847227
1848093


Hypothetical, unclassified, unknown
1848707
1849072


Hypothetical, unclassified, unknown
1849077
1849406


Protein secretion/export apparatus
1851982
1852278


Protein secretion/export apparatus
1855862
1856299


Hypothetical, unclassified, unknown
1856308
1856553


Protein secretion/export apparatus
1882558
1862761


Protein secretion/export apparatus
1862764
1863021


Protein secretion/export apparatus
1863024
1863371


Protein secretion/export apparatus
1863799
1864137


Hypothetical, unclassified, unknown
1874967
1875767


Hypothetical, unclassified, unknown
1875849
1876580


Hypothetical, unclassified, unknown
1887297
1887058


Hypothetical, unclassified, unknown
1888186
1887698


Hypothetical, unclassified, unknown
1889173
1888985


Amino acid biosynthesis and metabolism
1891815
1890739


Amino acid biosynthesis and metabolism
1896630
1897247


Hypothetical, unclassified, unknown
1912756
1912217


Biosynthesis of cofactors, prosthetic group
1917599
1918087


Transport of small molecules
1921174
1922226


Central intermediary metabolism
1926123
1925797


Transport of small molecules
1931775
1930564


Hypothetical, unclassified, unknown
1933632
1933054


Energy metabolism
1937644
1935035


Hypothetical, unclassified, unknown
1939583
1940206


Hypothetical, unclassified, unknown
1942442
1941720


Translation, post-translational modification
1943067
1944737


Translation, post-translational modification
1944747
1946129


Biosynthesis of cofactors, prosthetic group
1947041
1946187


Translation, post-translational modification
1956227
1958623


DNA replication, recombination, modification
1972959
1973405


Nucleotide biosynthesis and metabolism
1973470
1974210


Hypothetical, unclassified, unknown
1974627
1974238


Transport of small molecules
1979941
1978439


Hypothetical, unclassified, unknown
1984389
1985033


Hypothetical, unclassified, unknown
1989423
1989109


Hypothetical, unclassified, unknown
1993898
1993461


Hypothetical, unclassified, unknown
1995164
1994667


Hypothetical, unclassified, unknown
1998587
1998949


Hypothetical, unclassified, unknown
1999874
1999512


Hypothetical, unclassified, unknown
2004892
2004374


Hypothetical, unclassified, unknown
2007865
2008249


Hypothetical, unclassified, unknown
2012530
2012255


Hypothetical, unclassified, unknown
2015136
2014915


Transcriptional regulators
2019690
2018803


Transport of small molecules
2022398
2021712


Hypothetical, unclassified, unknown
2028454
2028981


Fatty acid and phospholipid metabolism
2031466
2031705


Hypothetical, unclassified, unknown
2034857
2034066


Transport of small molecules
2052941
2053264


Energy metabolism
2053277
2053675


Transcriptional regulators
2054223
2053672


Hypothetical, unclassified, unknown
2054309
2054842


Hypothetical, unclassified, unknown
2062401
2061664


Hypothetical, unclassified, unknown
2065545
2064853


Hypothetical, unclassified, unknown
2066767
2065493


Hypothetical, unclassified, unknown
2067955
2066786


Hypothetical, unclassified, unknown
2068728
2067961


Secreted Factors (toxins, enzymes, algin
2070685
2071173


Secreted Factors (toxins, enzymes, algin
2071209
2071697


Secreted Factors (toxins, enzymes, algin
2076311
2076958


Transcriptional regulators
2085426
2084476


Transcriptional regulators
2085929
2085423


Hypothetical, unclassified, unknown
2088034
2086808


Hypothetical, unclassified, unknown
2091837
2091490


Hypothetical, unclassified, unknown
2103294
2103770


Hypothetical unclassified, unknown
2103770
2104096


Translation, post-translational modification
2109511
2108942


Hypothetical, unclassified, unknown
2109854
2109558


Hypothetical, unclassified, unknown
2117897
2118097


Hypothetical, unclassified, unknown
2118585
2118893


Hypothetical, unclassified, unknown
2118926
2119747


Hypothetical, unclassified, unknown
2122222
2120225


Hypothetical, unclassified, unknown
2137785
2136520


Hypothetical, unclassified, unknown
2138598
2137846


Hypothetical, unclassified, unknown
2141002
2140433


Hypothetical, unclassified, unknown
2141487
2140999


Hypothetical, unclassified, unknown
2145894
2146502


Hypothetical, unclassified, unknown
2146609
2146875


Hypothetical, unclassified, unknown
2148855
2149189


Hypothetical, unclassified, unknown
2150364
2149864


Hypothetical, unclassified, unknown
2150524
2150781


Hypothetical, unclassified, unknown
2157968
2159167


Transcriptional regulators
2164548
2163883


Two-component regulatory systems
2165876
2166553


Biosynthesis of cofactors, prosthetic group
2171865
2171936


Prosthetic group
2171989
2172903


Biosynthesis of cofactors, prosthetic group
2173662
2173940


Hypothetical, unclassified, unknown
2181744
2181181


Hypothetical, unclassified, unknown
2182097
2181741


Chaperones & heat shock proteins
2182394
2182116


Fatty acid and phospholipid metabolism
2187065
2188246


Hypothetical, unclassified, unknown
2188459
2189883


Carbon compound catabolism
2196132
2195494


Transcriptional regulators
2198891
2199694


Putative enzymes
2203446
2202649


Fatty acid and phospholipid metabolism
2206353
2205190


Transcriptional regulators
2206806
2206402


Hypothetical, unclassified, unknown
2206999
2207928


Hypothetical, unclassified, unknown
2213539
2213315


Hypothetical, unclassified, unknown
2219099
2218098


Hypothetical, unclassified, unknown
2220275
2220574


Hypothetical, unclassified, unknown
2221157
2220903


Hypothetical, unclassified, unknown
2223804
2224478


Hypothetical, unclassified, unknown
2227541
2229001


Transport of small molecules
2234080
2235309


Transcriptional regulators
2244995
2245948


Central intermediary metabolism
2246456
2245986


Transport of small molecules
2256704
2257720


Putative enzymes
2259478
2260659


Hypothetical, unclassified, unknown
2265764
2265126


Translation, post-translational modification
2272460
2274568


Transport of small molecules
2277552
2278982


Hypothetical, unclassified, unknown
2278982
2279794


Hypothetical, unclassified, unknown
2281578
2279917


Hypothetical, unclassified, unknown
2290335
2289085


Hypothetical, unclassified, unknown
2297072
2297920


Hypothetical, unclassified, unknown
2300676
2301755


Transport of small molecules
2303022
2304215


Hypothetical, unclassified, unknown
2306627
2305782


Carbon compound catabolism
2307957
2309432


Hypothetical, unclassified, unknown
2312899
2313789


Biosynthesis of cofactors, prosthetic group
2314512
2315690


Putative enzymes
2316708
2317403


Hypothetical, unclassified, unknown
2318624
2318226


Hypothetical, unclassified, unknown
2322071
2321130


DNA replication, recombination, modification
2329348
2330424


Putative enzymes
2332059
2330959


Hypothetical, unclassified, unknown
2332820
2332392


Transcriptional regulators
2335172
2336104


Hypothetical, unclassified, unknown
2339987
2339352


Hypothetical, unclassified, unknown
2346477
2347838


Hypothetical, unclassified, unknown
2352430
2351906


Putative enzymes
2356713
2357573


Hypothetical, unclassified, unknown
2358024
2358311


Hypothetical, unclassified, unknown
2361706
2361873


Hypothetical, unclassified, unknown
2364816
2365058


Hypothetical, unclassified, unknown
2377476
2376538


Hypothetical, unclassified, unknown
2381778
2381473


Hypothetical, unclassified, unknown
2390255
2390620


Hypothetical, unclassified, unknown
2390949
2392046


Hypothetical, unclassified, unknown
2393424
2393633


Hypothetical, unclassified, unknown
2393708
2394178


Hypothetical, unclassified, unknown
2396252
2395944


Hypothetical, unclassified, unknown
2396883
2396536


Hypothetical, unclassified, unknown
2404655
2404386


Hypothetical, unclassified, unknown
2405233
2404949


Hypothetical, unclassified, unknown
2405739
2405230


Hypothetical, unclassified, unknown
2405993
2406877


Hypothetical, unclassified, unknown
2406961
2407131


Hypothetical, unclassified, unknown
2407236
2407661


Hypothetical, unclassified, unknown
2409837
2410181


Hypothetical, unclassified, unknown
2411709
2412122


Transcriptional regulators
2415661
2416245


Hypothetical, unclassified, unknown
2416376
2417413


Hypothetical, unclassified, unknown
2424400
2423924


Hypothetical, unclassified, unknown
2427017
2425497


Hypothetical, unclassified, unknown
2430170
2431129


Transport of small molecules
2433748
2435070


Transport of small molecules
2441555
2440347


Transcriptional regulators
2441771
2442691


Hypothetical, unclassified, unknown
2443161
2444366


Hypothetical, unclassified, unknown
2445533
2444886


Hypothetical, unclassified, unknown
2446564
2445545


Hypothetical, unclassified, unknown
2447325
2446597


Hypothetical, unclassified, unknown
2447989
2447573


Hypothetical, unclassified, unknown
2448533
2448033


Transcriptional regulators
2449545
2448568


Hypothetical, unclassified, unknown
2450765
2449554


Hypothetical, unclassified, unknown
2451707
2452426


Transport of small molecules
2457510
2458280


Hypothetical, unclassified, unknown
2468032
2469099


Hypothetical, unclassified, unknown
2472104
2472409


Hypothetical, unclassified, unknown
2479130
2478312


Amino acid biosynthesis and metabolism
2480844
2481830


Secreted Factors (toxins, enzymes, algina
2485471
2486118


Transcriptional regulators
2487293
2486355


Hypothetical, unclassified, unknown
2488950
2489732


Hypothetical, unclassified, unknown
2508775
2509467


Hypothetical, unclassified, unknown
2510622
2511050


Hypothetical, unclassified, unknown
2512511
2513182


Hypothetical, unclassified, unknown
2523239
2522958


Hypothetical, unclassified, unknown
2524201
2523236


Transport of small molecules
2525052
2524198


Transport of small molecules
2525846
2525049


Energy metabolism
2527657
2527412


Putative enzymes
2529467
2527743


Hypothetical, unclassified, unknown
2540082
2539063


Hypothetical, unclassified unknown
2549748
2549906


Transcriptional regulators
2553965
2554858


Transport of small molecules
2571691
2570855


Hypothetical, unclassified, unknown
2573365
2572805


Hypothetical, unclassified, unknown
2579542
2580882


Transport of small molecules
2582097
2583407


Carbon compound catabolism
2587906
2589414


Hypothetical, unclassified, unknown
2593330
2594547


Hypothetical, unclassified, unknown
2595985
2596779


Transport of small molecules
2597869
2598522


Hypothetical, unclassified, unknown
2614893
2615438


Hypothetical, unclassified, unknown
2617019
2617516


Hypothetical, unclassified, unknown
2617529
2617954


Hypothetical, unclassified, unknown
2619695
2620711


Hypothetical, unclassified, unknown
2623284
2623856


Hypothetical, unclassified, unknown
2627175
2626780


Transcriptional regulators
2635971
2636051


Transport of small molecules
2645303
2646727


Hypothetical, unclassified, unknown
2689240
2689569


Hypothetical, unclassified, unknown
2689566
2690126


Putative enzymes
2694544
2693780


Hypothetical, unclassified, unknown
2694763
2694545


Hypothetical, unclassified, unknown
2701205
2702065


Hypothetical, unclassified, unknown
2705772
2706086


Hypothetical, unclassified, unknown
2723221
2722754


Hypothetical, unclassified, unknown
2724222
2723308


Hypothetical, unclassified, unknown
2724484
2724729


Hypothetical, unclassified, unknown
2730520
2729975


Hypothetical, unclassified, unknown
2732965
2732531


Hypothetical, unclassified, unknown
2738840
2739715


Amino acid biosynthesis and metabolism
2740882
2739761


Amino acid biosynthesis and metabolism
2747072
2746689


Hypothetical, unclassified, unknown
2753464
2752865


Hypothetical, unclassified, unknown
2754601
2754822


Hypothetical, unclassified, unknown
2755724
2754851


Hypothetical, unclassified, unknown
2756308
2756649


Hypothetical, unclassified, unknown
2760086
2759481


Hypothetical, unclassified, unknown
2760618
2760322


Hypothetical, unclassified, unknown
2761350
2760871


Hypothetical, unclassified, unknown
2781450
2780926


Transcriptional regulators
2786355
2785369


Transcriptional regulators
2787885
2786971


Central intermediary metabolism
2791219
2791863


Hypothetical, unclassified, unknown
2791905
2792816


Putative enzymes
2794132
2792798


Hypothetical, unclassified, unknown
2803344
2803622


Hypothetical, unclassified, unknown
2804131
2803859


Hypothetical, unclassified, unknown
2805916
2806290


Putative enzymes
2807368
2806349


Transcriptional regulators
2807468
2808511


Hypothetical, unclassified, unknown
2815281
2814766


Transport of small molecules
2817448
2818674


Hypothetical, unclassified, unknown
2818885
2818718


Hypothetical, unclassified, unknown
2822321
2821704


Carbon compound catabolism
2825590
2824658


Carbon compound catabolism
2833129
2832368


Carbon compound catabolism
2834689
2834201


Transport of small molecules
2841965
2840511


Fatty acid and phospholipid metabolism
2865104
2864169


Hypothetical, unclassified, unknown
2866199
2865747


Hypothetical, unclassified, unknown
2867505
2866192


Hypothetical, unclassified, unknown
2876409
2875696


Hypothetical, unclassified, unknown
2880519
2881562


Transcriptional regulators
2883156
2884088


Putative enzymes
2885332
2884205


Putative enzymes
2886551
2885361


Putative enzymes
2887336
2886569


Transcriptional regulators
2913921
2914358


Fatty acid and phospholipid metabolism
2923926
2923366


Transcriptional regulators
2934387
2933581


Hypothetical, unclassified, unknown
2945263
2945868


Hypothetical, unclassified, unknown
2948581
2948976


Hypothetical, unclassified, unknown
2948973
2949332


Hypothetical, unclassified, unknown
2949332
2949637


Hypothetical, unclassified, unknown
2949634
2949969


Translation, post-translational modification
2954695
2953415


Chaperones & heat shock proteins
2956778
2956152


Cell division
2959239
2956804


Translation, post-translational modification
2960455
2961135


Translation, post-translational modification
2962002
2962220


Hypothetical, unclassified, unknown
2964842
2964606


transcription, RNA processing and degr
2969986
2971113


Nucleotide biosynthesis and metabolism
2972698
2974068


Energy metabolism
2983204
2983881


Energy metabolism
2986242
2987588


Energy metabolism
2992001
2992501


Energy metabolism
2992547
2992855


Hypothetical, unclassified, unknown
3008323
3008009


Hypothetical, unclassified, unknown
3012536
3012279


Biosynthesis of cofactors, prosthetic grout
3015581
3015937


Hypothetical, unclassified, unknown
3016245
3016598


Hypothetical, unclassified, unknown
3016883
3016674


Protein secretion/export apparatus
3020928
3020503


Protein secretion/export apparatus
3021338
3020928


Protein secretion/export apparatus
3021741
3021307


Transport of small molecules
3025507
3024704


Transcriptional regulators
3028074
3029003


Amino acid biosynthesis and metabolism
3031397
3030435


Hypothetical, unclassified, unknown
3042501
3043415


Related to phage, transposon, or plasmid
3044765
3043749


Energy metabolism
3047969
3047643


Hypothetical, unclassified, unknown
3050611
3050330


Hypothetical, unclassified, unknown
3057375
3057608


Hypothetical, unclassified, unknown
3060659
3060264


Energy metabolism
3070365
3070703


Hypothetical, unclassified, unknown
3073731
3074417


Hypothetical, unclassified, unknown
3075217
3074579


Hypothetical, unclassified, unknown
3075410
3075889


Hypothetical, unclassified, unknown
3075921
3076313


Hypothetical, unclassified, unknown
3076343
3076621


Central intermediary metabolism
3079196
3079834


Hypothetical, unclassified, unknown
3089612
3088659


Hypothetical, unclassified, unknown
3090107
3089643


Hypothetical, unclassified, unknown
3094184
3093657


Hypothetical, unclassified, unknown
3096051
3094756


Hypothetical, unclassified, unknown
3098978
3098625


Hypothetical, unclassified, unknown
3099729
3099472


DNA replication, recombination, modification
3100111
3099809


Translation, post-translational modification
3102493
3100115


Translation, post-translational modification
3103544
3102528


Translation, post-translational modification
3103998
3103642


Translation, post-translational modification
3104216
3104022


Translation, post-translational modification
3104829
3104278


Translation, post-translational modification
3106751
3104829


DNA replication, recombination, modification
3110900
3111613


Hypothetical, unclassified, unknown
3114818
3115192


Hypothetical, unclassified, unknown
3117610
3117176


Hypothetical, unclassified, unknown
3119707
3119393


Hypothetical, unclassified, unknown
3122264
3121920


Hypothetical, unclassified, unknown
3122585
3122376


Putative enzymes
3126251
3127219


Hypothetical, unclassified, unknown
3127225
3127707


Hypothetical, unclassified, unknown
3128269
3127859


Hypothetical, unclassified, unknown
3132815
3132228


Hypothetical, unclassified, unknown
3133257
3132820


Hypothetical, unclassified, unknown
3137849
3138193


Hypothetical, unclassified, unknown
3138190
3138531


Hypothetical, unclassified, unknown
3139010
3139669


Hypothetical, unclassified, unknown
3141718
3142275


Hypothetical, unclassified, unknown
3142284
3142502


Hypothetical, unclassified, unknown
3142617
3143084


Hypothetical, unclassified, unknown
3149318
3148722


Hypothetical, unclassified, unknown
3152201
3150885


Hypothetical, unclassified, unknown
3155074
3154592


Hypothetical, unclassified, unknown
3156502
3156801


Hypothetical, unclassified, unknown
3157563
3156859


Hypothetical, unclassified, unknown
3158925
3159668


Hypothetical, unclassified, unknown
3160320
3160583


Hypothetical, unclassified, unknown
3162215
3161598


Hypothetical, unclassified, unknown
3162578
3162387


Transport of small molecules
3165541
3164762


Hypothetical, unclassified, unknown
3173174
3171597


Hypothetical, unclassified, unknown
3173243
3173722


Hypothetical, unclassified, unknown
3180951
3180553


Hypothetical, unclassified, unknown
3182399
3182851


Hypothetical, unclassified, unknown
3184001
3185128


Adaptation, protection
3185816
3185160


Hypothetical, unclassified, unknown
3192748
3193518


Putative enzymes
3197641
3198987


Hypothetical, unclassified, unknown
3200552
3200319


Translation, post-translational modification
3205079
3204513


Hypothetical, unclassified, unknown
3206252
3205122


Membrane proteins
3206914
3207165


Hypothetical, unclassified, unknown
3208260
3207289


Transcription, RNA processing and degr
3212524
3213030


Secreted Factors (toxins, enzymes, algina
3215422
3216288


Hypothetical, unclassified, unknown
3221205
3221564


Hypothetical, unclassified, unknown
3228336
3227383


Nucleotide biosynthesis and metabolism
3230181
3229483


Transcriptional regulators
3231171
3230278


Transcriptional regulators
3232771
3231881


Hypothetical, unclassified, unknown
3235793
3235960


Hypothetical, unclassified, unknown
3249630
3249208


Hypothetical, unclassified, unknown
3253679
3253311


Hypothetical, unclassified, unknown
3255765
3255406


Hypothetical, unclassified, unknown
3265210
3264641


Hypothetical, unclassified, unknown
3271692
3270826


Hypothetical, unclassified, unknown
3272405
3271812


Putative enzymes
3277408
3278577


Hypothetical, unclassified, unknown
3284597
3283374


Hypothetical, unclassified, unknown
3291172
3290693


Hypothetical, unclassified, unknown
3291282
3291863


Hypothetical, unclassified, unknown
3291959
3292267


Putative enzymes
3297117
3295978


Putative enzymes
3308390
3309337


Energy metabolism
3311720
3310791


Energy metabolism
3312469
3311720


Energy metabolism
3312790
3314445


Motility & Attachment
3320029
3319673


DNA replication, recombination, modification
3321049
3320063


Nucleotide biosynthesis and metabolism
3321674
3321042


Hypothetical, unclassified, unknown
3322752
3321703


Fatty acid and phospholipid metabolism
3325182
3324946


Fatty acid and phospholipid metabolism
3326121
3325378


Fatty acid and phospholipid metabolism
3327082
3326144


Translation, post-translational modification
3328384
3328202


Hypothetical, unclassified, unknown
3328934
3328398


Transcription, RNA processing and degr
3332303
3331347


Cell wall / LPS / capsule
3337230
3336211


Translation, post-translational modification
3337691
3337227


Cell wall / LPS / capsule
3338455
3337691


Hypothetical, unclassified, unknown
3338640
3338455


Cell wall / LPS / capsule
3339676
3338678


Hypothetical, unclassified, unknown
3340116
3339676


Transport of small molecules
3340748
3340113


Hypothetical, unclassified, unknown
3343177
3343710


Hypothetical, unclassified, unknown
3345099
3343798


Transport of small molecules
3345795
3345112


Hypothetical, unclassified, unknown
3347038
3345788


Hypothetical, unclassified, unknown
3346976
3347740


Nucleotide biosynthesis and metabolism
3350231
3348837


Hypothetical, unclassified, unknown
3350637
3350410


Energy metabolism
3354171
3353497


Putative enzymes
3360653
3359268


Nucleotide biosynthesis and metabolism
3365743
3365006


Hypothetical, unclassified, unknown
3369268
3369035


DNA replication, recombination, modification
3372705
3370099


Hypothetical, unclassified, unknown
3373170
3372796


Hypothetical, unclassified, unknown
3378511
3378948


Hypothetical, unclassified, unknown j
3383947
3384333


Hypothetical, unclassified, unknown
3385183
3384377


Putative enzymes
3387828
3386269


Biosynthesis of cofactors, prosthetic group
3394087
3394683


Hypothetical, unclassified, unknown
3397373
3397095


Hypothetical, unclassified, unknown
3398716
3399648


Hypothetical, unclassified, unknown
3403811
3404140


Hypothetical, unclassified, unknown
3404144
3404524


Hypothetical, unclassified, unknown
3404538
3404861


Hypothetical, unclassified, unknown
3409952
3409608


Translation, post-translational modification
3414400
3414612


Hypothetical, unclassified, unknown
3416066
3415785


Transcriptional regulators
3436429
3435986


Hypothetical, unclassified, unknown
3457909
3456542


Hypothetical, unclassified, unknown
3464151
3463888


Hypothetical unclassified, unknown
3466959
3466072


Hypothetical, unclassified, unknown
3467084
3468049


Hypothetical, unclassified, unknown
3473017
3474135


Protein secretion/export apparatus
3476479
3475955


Protein secretion/export apparatus
3477629
3476481


Protein secretion/export apparatus
3480238
3479720


Protein secretion/export apparatus
3483421
3481913


Hypothetical, unclassified, unknown
3491410
3490751


Fatty acid and phospholipid metabolism
3493572
3492700


Amino acid biosynthesis and metabolism
3500597
3499485


Hypothetical, unclassified, unknown
3506241
3505864


Hypothetical, unclassified, unknown
3524489
3524160


Hypothetical, unclassified, unknown
3527733
3527428


Hypothetical, unclassified, unknown
3528349
3528230


Cell wall / LPS / capsule
3529446
3528427


Cell wall / LPS / capsule
3530457
3529507


Cell wall / LPS / capsule
3531707
3530466


Cell wall / LPS / capsule
3532814
3531750


Cell wall / LPS / capsule
3533932
3532811


Cell wall / LPS / capsule
3535080
3533947


Amino acid biosynthesis and metabolism
3535970
3535215


Amino acid biosynthesis and metabolism
3536578
3535970


Cell wall / LPS / capsule
3537810
3536575


Cell wall / LPS / capsule
3539123
3537807


Cell wall / LPS / capsule
3540206
3539127


Cell wall / LPS / capsule
3540784
3540209


Cell wall / LPS / capsule
3542670
3540781


Cell wall / LPS / capsule
3543689
3542739


Cell wall / LPS / capsule
3545073
3543763


Cell wall / LPS / capsule
3546926
3545880


DNA replication, recombination, modification
3547972
3547688


Translation, post-translational modification
3549788
3548109


Nucleotide biosynthesis and metabolism
3550745
3550056


Biosynthesis of cofactors, prosthetic group
3556338
3555253


DNA replication, recombination, modification
3559197
3556426


Biosynthesis of cofactors, prosthetic group
3562105
3562803


Hypothetical, unclassified, unknown
3569012
3568635


Carbon compound catabolism
3571602
3570940


Hypothetical, unclassified, unknown
3575696
3574845


Carbon compound catabolism
3587432
3588436


Hypothetical, unclassified, unknown
3593732
3594031


Hypothetical, unclassified, unknown
3594207
3594569


Hypothetical, unclassified, unknown
3597318
3597797


Transport of small molecules
3600453
3601598


Transcriptional regulators
3609075
3609839


Chaperones & heat shock proteins
3614303
3614866


Hypothetical, unclassified, unknown
3618466
3617342


Putative enzymes
3619618
3618992


Hypothetical, unclassified, unknown
3624836
3625057


Cell wall / LPS / capsule
3630604
3629666


Cell division
3632429
3632683


Transcription, RNA processing and degr
3632787
3633422


Transcriptional regulators
3636256
3635540


Hypothetical, unclassified, unknown
3641232
3641810


Transcriptional regulators
3648065
3647754


Adaptation, protection
3653666
3653875


Hypothetical, unclassified, unknown
3668522
3667923


Hypothetical, unclassified, unknown
3668473
3668760


Hypothetical, unclassified, unknown
3669168
3668839


Hypothetical, unclassified, unknown
3671057
3670758


Transport of small molecules
3674323
3673007


Hypothetical, unclassified, unknown
3675159
3674569


Hypothetical, unclassified, unknown
3679945
3680460


Hypothetical, unclassified, unknown
3680967
3680464


Hypothetical, unclassified, unknown
3681047
3681460


Hypothetical, unclassified, unknown
3684716
3684162


Hypothetical, unclassified, unknown
3685761
3684904


Hypothetical, unclassified, unknown
3695480
3695178


Hypothetical, unclassified, unknown
3700315
3700785


Hypothetical, unclassified, unknown
3710224
3710679


Putative enzymes
3715804
3714914


Transport of small molecules
3716807
3717610


Transport of small molecules
3717604
3718437


Hypothetical, unclassified, unknown
3719328
3720056


Hypothetical, unclassified, unknown
3720122
3720622


Hypothetical, unclassified, unknown
3723444
3722989


Translation, post-translational modification
3730075
3729470


Putative enzymes
3740104
3741018


Hypothetical, unclassified, unknown
3742264
3742689


Fatty acid and phospholipid metabolism
3743699
3743938


Hypothetical, unclassified, unknown
3747455
3747165


Transcriptional regulators
3752477
3752043


Hypothetical, unclassified, unknown
3759680
3759375


Chemotaxis
3760819
3759995


Hypothetical, unclassified, unknown
3762803
3763126


Hypothetical, unclassified, unknown
3763680
3764471


Hypothetical, unclassified, unknown
3765086
3764475


Secreted Factors (toxins, enzymes, algina
3772560
3771502


Hypothetical, unclassified, unknown
3778265
3778603


Putative enzymes
3778703
3779368


Hypothetical, unclassified, unknown
3779929
3780075


Hypothetical, unclassified, unknown
3780127
3780312


Hypothetical, unclassified, unknown
3787478
3787020


Transport of small molecules
3790985
3790149


Hypothetical unclassified, unknown
3794116
3793814


Energy metabolism
3801103
3801930


Energy metabolism
3801947
3802483


Energy metabolism
3803342
3802566


Hypothetical, unclassified, unknown
3808802
3808317


Transport of small molecules
3814574
3813957


Hypothetical, unclassified, unknown
3820005
3820271


Hypothetical, unclassified, unknown
3820307
3820891


Energy metabolism
3823515
3822514


Hypothetical, unclassified, unknown
3840747
3840358


Transcriptional regulators
3840843
3841736


Related to phage, transposon, or plasmid
3843289
3842273


Hypothetical, unclassified, unknown
3844104
3843652


Biosynthesis of cofactors, prosthetic group
3845774
3846334


Biosynthesis of cofactors, prosthetic group
3846336
3846707


Transport of small molecules
3849582
3848794


Hypothetical, unclassified, unknown
3850751
3849603


Hypothetical, unclassified, unknown
3851800
3850829


Hypothetical, unclassified, unknown
3852512
3851919


Adaptation, protection
3856130
3855492


Hypothetical, unclassified, unknown
3856336
3856545


Putative enzymes
3867706
3869463


Hypothetical, unclassified, unknown
3882979
3883437


Hypothetical, unclassified, unknown
3885710
3886306


Transcriptional regulators
3890649
3889924


Translation, post-translational modification
3895323
3897356


Hypothetical, unclassified, unknown
3906390
3907088


Hypothetical, unclassified, unknown
3907267
3907851


Hypothetical, unclassified, unknown
3910738
3911772


Hypothetical, unclassified, unknown
3912409
3913131


DNA replication, recombination, modification
3913128
3913766


Hypothetical, unclassified, unknown
3913875
3914054


Hypothetical, unclassified, unknown
3918468
3918250


Hypothetical, unclassified, unknown
3918787
3918470


Hypothetical, unclassified, unknown
3922072
3921269


Transport of small molecules
3928333
3927557


Hypothetical, unclassified, unknown
3936836
3935799


Hypothetical, unclassified, unknown
3937431
3937237


Transport of small molecus
3943806
3942649


Transcription, RNA processing and degra
3948137
3948811


Hypothetical unclassified, unknown
3949852
3950073


Hypothetical, unclassified, unknown
3952386
3952060


Secreted Factors (toxins, enzymes, algina
3965841
3967010


Secreted Factors (toxins, enzymes, algina
3977183
3977833


Hypothetical, unclassified, unknown
3986879
3937292


Hypothetical, unclassified, unknown
3997821
3998114


Carbon compound catabolism
4003600
4002107


Hypothetical, unclassified, unknown
4004782
4004958


Hypothetical, unclassified, unknown
4007506
4008036


Hypothetical, unclassified, unknown
4010326
4009541


Carbon compound catabolism
4023176
4021971


Hypothetical, unclassified, unknown
4035757
4035605


Hypothetical, unclassified, unknown
4036020
4035757


Hypothetical, unclassified, unknown
4039173
4040099


Hypothetical, unclassified, unknown
4040819
4040103


Transport of small molecules
4043060
4043830


Hypothetical, unclassified, unknown
4045159
4045569


Hypothetical, unclassified, unknown
4045588
4045809


Hypothetical, unclassified, unknown
4051557
4051096


DNA replication, recombination, modification
4052603
4051563


Hypothetical, unclassified, unknown
4062898
4062425


Hypothetical, unclassified, unknown
4067294
4067542


Hypothetical, unclassified, unknown
4068307
4067603


Hypothetical, unclassified, unknown
4068611
4068327


Carbon compound catabolism
4069961
4068676


Cell wall / LPS / capsule
4070856
4070011


Nucleotide biosynthesis and metabolism
4072487
4070859


Hypothetical, unclassified, unknown
4073986
4072658


Fatty acid and phospholipid metabolism
4075006
4074056


DNA replication, recombination, modification
4078677
4075156


Cell wall / LPS / capsule
4082180
4081044


Cell wall / LPS / capsule
4082960
4082184


Fatty acid and phospholipid metabolism
4083397
4082957


Cell wall / LPS / capsule
4084504
4083443


Transport of small molecules
4085010
4084504


Transport of small molecules
4087454
4085061


Biosynthesis of cofactors, prosthetic group
4090093
4088903


Fatty acid and phospholipid metabolism
4090905
4090090


Cell wall / LPS / capsule
4091654
4090899


Translation, post-translational modification
4092227
4091670


Nucleotide biosynthesis and metabolism
4092967
4092230


Translation, post-translational modification
4094035
4093166


Translation, post-translational modification
4094906
4094166


Translation, post-translational modification
4095171
4095956


Hypothetical, unclassified, unknown
4102767
4103060


Hypothetical, unclassified, unknown
4103731
4104078


Cell wall / LPS / capsule
4104744
4105778


Transport of small molecules
4111080
4110346


Hypothetical, unclassified, unknown
4114932
4115330


Transcriptional regulators
4120468
4121106


Hypothetical, unclassified, unknown
4123955
4123260


Hypothetical, unclassified, unknown
4126089
4125742


Hypothetical, unclassified, unknown
4126843
4126163


Hypothetical, unclassified, unknown
4130598
4130942


Hypothetical, unclassified, unknown
4135972
4135451


Translation, post-translational modification
4143664
4142569


Chemotaxis
4148251
4145942


Hypothetical, unclassified, unknown
4165879
4165718


DNA replication, recombination, modification
4172484
4170769


Hypothetical, unclassified, unknown
4173067
4172528


Hypothetical, unclassified, unknown
4182018
4181377


Hypothetical, unclassified, unknown
4182769
4182074


Hypothetical, unclassified, unknown
4183709
4184938


Translation, post-translational modification
4195357
4195007


Transcription, RNA processing and degra
4196157
4195399


Transcription, RNA processing and degra
4196691
4196164


Translation, post-translational modification
4196958
4196707


Protein secretion/export apparatus
4198541
4197168


Hypothetical, unclassified, unknown
4204736
4204542


Hypothetical, unclassified, unknown
4205906
4205295


Hypothetical, unclassified, unknown
4206664
4207164


Putative enzymes
4209255
4210277


Hypothetical, unclassified, unknown
4221796
4221212


Hypothetical, unclassified, unknown
4224115
4223567


Nucleotide biosynthesis and metabolism
4227236
4225659


Hypothetical, unclassified, unknown
4231070
4232227


Transcriptional regulators
4234274
4235182


DNA replication, recombination, modification
4235219
4236598


Transcriptional regulators
4242294
4241341


Hypothetical, unclassified, unknown
4243651
4243079


Hypothetical, unclassified, unknown
4244184
4243708


Hypothetical, unclassified, unknown
4244875
4245723


Hypothetical, unclassified, unknown
4245809
4246204


Hypothetical, unclassified, unknown
4255323
4254736


Hypothetical, unclassified, unknown
4260396
4259254


Hypothetical, unclassified, unknown
4263492
4262377


Motility & Attachment
4265287
4264629


Hypothetical, unclassified, unknown
4256444
4265305


Nucleotide biosynthesis and metabolism
4266900
4266469


Hypothetical, unclassified, unknown
4267344
4267144


Energy metabolism
4267709
4267371


Chaperones & heat shock proteins
4269575
4267716


Chaperones & heat shock proteins
4270139
4269618


Biosynthesis of cofactors, prosthetic group
4270470
4270147


Biosynthesis of cofactors, prosthetic group
4270884
4270498


Hypothetical, unclassified, unknown
4272655
4272164


Protein secretion/export apparatus
4278945
4277084


Hypothetical, unclassified, unknown
4279344
4279006


Hypothetical, unclassified, unknown
4285483
4284416


Hypothetical, unclassified, unknown
4286594
4285476


Hypothetical, unclassified, unknown
4287709
4286786


Hypothetical, unclassified, unknown
4290866
4291234


Translation, post-translational modification
4291355
4294207


Hypothetical, unclassified, unknown
4294604
4294254


Hypothetical, unclassified, unknown
4302040
4303050


Hypothetical, unclassified, unknown
4305063
4305425


Hypothetical, unclassified, unknown
4311861
4310950


Hypothetical, unclassified, unknown
4312702
4311950


Hypothetical, unclassified, unknown
4314794
4314480


Hypothetical, unclassified, unknown
4316037
4315555


Hypothetical, unclassified, unknown
4316824
4316108


Putative enzymes
4318258
4318905


DNA replication, recombination, modficat
4330320
4330895


Hypothetical, unclassified, unknown
4331451
4332461


Hypothetical, unclassified, unknown
4332652
4333035


Transport of small molecules
4343527
4342121


Hypothetical, unclassified, unknown
4350352
4350738


Hypothetical, unclassified, unknown
4351594
4352493


Transport of small molecules
4354543
4355265


Transport of small molecules
4356200
4356862


Transport of small molecules
4356875
4358038


Hypothetical, unclassified, unknown
4359074
4358166


Hypothetical, unclassified, unknown
4373937
4374332


Hypothetical, unclassified, unknown
4374329
4374856


Hypothetical, unclassified, unknown
4374849
4375232


Hypothetical, unclassified, unknown
4382015
4381500


Biosynthesis of cofactors, prosthetic group
4386351
4385899


Biosynthesis of cofactors, prosthetic group
4386607
4386356


Biosynthesis of cofactors, prosthetic group
4387086
4386604


Transport of small molecules
4414949
4414131


NA replication, recombination, modification
4418302
4418583


Hypothetical, unclassified, unknown
4439376
4439783


Hypothetical, unclassified, unknown
4442452
4442868


Transcriptional regulators
4444977
4445486


Hypothetical, unclassified, unknown
4445998
4446390


Hypothetical, unclassified, unknown
4447132
4448217


Transcriptional regulators
4453182
4452535


Biosynthesis of cofactors, prosthetic group
4457361
4458644


Hypothetical, unclassified, unknown
4459749
4459417


Hypothetical, unclassified, unknown
4461387
4462409


Hypothetical, unclassified, unknown
4462399
4462881


Translation, post-translational modification
4463903
4465438


Hypothetical, unclassified, unknown
4466753
4466322


Translation, post-translational modification
4466924
4469545


Hypothetical, unclassified, unknown
4469612
4470235


DNA replication, recombination, modification
4470273
4471310


Hypothetical, unclassified, unknown
4471402
4471554


Related to phage, transposon, or plasmid
4473622
4474638


Biosynthesis of cofactors, prosthetic group
4477976
4476993


Hypothetical, unclassified, unknown
4478907
4478626


Cell wall / LPS / capsule
4483363
4482260


Hypothetical, unclassified, unknown
4486179
4485823


Hypothetical, unclassified, unknown
4486846
4486202


Putative enzymes
4488409
4489632


Secreted Factors (toxins, enzymes, algina
4713795
4714283


Secreted Factors (toxins, enzymes, algina
4714313
4714801


Secreted Factors (toxins, enzymes, algin
4714825
4716042


Secreted Factors (toxins, enzymes, algin
4718556
4719392


Secreted Factors (toxins, enzymes, algina
4719418
4720062


Hypothetical, unclassified, unknown
4724034
4722850


Transport of small molecules
4744818
4745123


DNA replication, recombination, modification
4747136
4746639


Translation, post-translational modification
4754378
4753989


Transcription, RNA processing and degra
4755423
4754422


Translation, post-translational modification
4756066
4755446


Translation, post-translational modification
4756472
4756083


Translation, post-translational modification
4756847
4756491


Translation, post-translational modification
4757094
4756978


Protein secretion/export apparatus
4758451
4757123


Translation, post-translational modification
4758886
4758452


Translation, post-translational modification
4759066
4758890


Translation, post-translational modification
4759569
4759069


Translation, post-translational modification
4759923
4759573


Translation, post-translational modification
4760467
4759934


Translation, post-translational modification
4760871
4760479


Translation, post-translational modification
4761366
4761061


Translation, post-translational modification
4761919
4761380


Translation, post-translational modification
4762253
4761939


Translation, post-translational modification
4762634
4762266


Translation, post-translational modification
4762924
4762658


Translation, post-translational modification
4763118
4762927


Translation, post-translational modification
4763531
4763118


Translation, post-translational modification
4764229
4763543


Translation, post-translational modification
4764574
4764242


Translation, post-translational modification
4764862
4764587


Translation, post-translational modification
4765700
4764879


Translation, post-translational modification
4766011
4765712


Translation, post-translational modification
4766610
4766008


Translation, post-translational modification
4767259
4766624


Translation, post-translational modification
4767653
4767342


Translation, post-translational modification
4771655
4771185


Translation, post-translational modification
4772126
4771755


Transcription, RNA processing and degr
4776477
4772278


Transcription, RNA processing and degr
4780616
4776543


Translation, post-translational modification
4781206
4780838


Translation, post-translational modification
4781785
4781285


Translation, post-translational modification
4782679
4781984


Translation, post-translational modification
4783110
4782679


Transcription, RNA processing and dea
4783760
4783227


Protein secretion/export apparatus
4784138
4783770


Hypothetical, unclassified, unknown
4787479
4786733


Hypothetical, unclassified, unknown
4819927
4820409


Two-component regulatory systems
4820531
4821358


Hypothetical, unclassified, unknown
4823363
4823079


Hypothetical, unclassified, unknown
4824123
4823386


Hypothetical, unclassified, unknown
4830553
4829642


Hypothetical, unclassified, unknown
4830963
4831181


Nucleotide biosynthesis and metabolism
4843551
4842700


Hypothetical, unclassified, unknown
4851309
4852316


Hypothetical, unclassified, unknown
4854008
4853649


Carbon compound catabolism
4856959
4858410


Putative enzymes
4859262
4858489


Transcriptional regulators
4870327
4869557


Hypothetical, unclassified, unknown
4875244
4874654


Hypothetical, unclassified, unknown
4877605
4876820


Hypothetical, unclassified, unknown
4878586
4877690


Hypothetical, unclassified, unknown
4878789
4879544


Hypothetical, unclassified, unknown
4882052
4882354


Hypothetical, unclassified, unknown
4884960
4884718


Hypothetical, unclassified, unknown
4887505
4887278


Adaptation, protection
4893696
4894277


Hypothetical, unclassified, unknown
4902201
4903295


Hypothetical, unclassified, unknown
4909403
4909161


Hypothetical, unclassified, unknown
4914509
4914126


Chaperones & heat shock proteins
4917123
4915480


Chaperones & heat shock proteins
4917467
4917174


Hypothetical, unclassified, unknown
4918932
4918198


Putative enzymes
4919041
4919799


Hypothetical, unclassified, unknown
4921980
4922363


Hypothetical, unclassified, unknown
4925794
4925315


protein secretion/export apparatus
4936615
4933865


Hypothetical, unclassified, unknown
4937819
4938214


Cell wall / LPS / capsule
4939186
4938275


Cell division
4940483
4939299


Cell division
4941787
4940534


Cell division
4942672
4941809


Cell wall LPS / capsule
4945074
4943632


Cell wall LPS / capsule
4946140
4945067


Cell division
4947329
4946130


Cell wall / LPS / capsule
4948675
4947329


Cell wall / LPS / capsule
4949771
4948689


Cell wall / LPS / capsule
4951147
4949771


Cell wall / LPS / capsule
4952603
4951140


Cell wall / LPS / capsule
4954342
4952603


Cell division
4954632
4954339


Hypothetical, unclassified, unknown
4955570
4954629


Hypothetical, unclassified, unknown
4956028
4955573


Hypothetical, unclassified, unknown
4959519
4959896


Putative enzymes
4959925
4960518


Adaptation, protection
4961557
4961150


Adaptation, protection
4962186
4961569


Energy metabolism
4964265
4963054


Translation, post-translational modification
4965500
4965108


Translation, post-translational modification
4965943
4965515


Transcriptional regulators
4968711
4969610


Hypothetical, unclassified, unknown
4971890
4970796


Translation, post-translational modification
4973331
4971985


Hypothetical, unclassified, unknown
4974028
4973399


Cell wall / LPS / capsule
4985469
4984204


Hypothetical, unclassified, unknown
4986154
4985846


Hypothetical, unclassified, unknown
4986798
4986151


Hypothetical, unclassified, unknown
4987283
4986810


Transport of small molecules
4988081
4987284


Hypothetical, unclassified, unknown
4989304
4990284


Hypothetical, unclassified, unknown
4990832
4991404


Hypothetical, unclassified, unknown
4991391
4991918


Transport of small molecules
4991918
4992643


Transcriptional regulators
4992869
4994362


Hypothetical, unclassified, unknown
4994440
4994748


Transport of small molecules
4994762
4995226


Transport of small molecules
4996118
4996390


Hypothetical, unclassified, unknown
5000303
4999908


Cell division
5012313
5011321


Cell division
5013430
5012393


Translation, post-translational modification
5013670
5013960


Translation, post-translational modification
5013973
5015427


Translation, post-translational modification
5015534
5016979


Hypothetical, unclassified, unknown
5017039
5017416


Hypothetical, unclassified, unknown
5028230
5027421


Transcriptional regulators
5036244
5036807


Hypothetical, unclassified, unknown
5046663
5046031


Biosynthesis of cofactors, prosthetic group
5068031
5068879


Motility & Attachment
5069530
5069081


Motility & Attachment
5069762
5071462


Motility & Attachment
5071566
5072690


Hypothetical, unclassified, unknown
5073563
5074174


Hypothetical, unclassified, unknown
5074171
5074371


Hypothetical, unclassified, unknown
5077535
5077705


Transcription, RNA processing and degr
5091814
5090852


Two-component regulatory systems
5094984
5096321


Motility & Attachment
5099262
5100086


Motility & Attachment
5100083
5100670


Adaptation, protection
5105929
5104985


Translation, post-translational modification
5106957
5106448


Translation, post-translational modification
5109781
5106950


Biosynthesis of cofactors, prosthetic group
5110743
5109805


Translation, post-translational modification
5112662
5112937


Hypothetical, unclassified, unknown
5113468
5113004


Amino acid biosynthesis and metabolism
5114598
5113480


Adaptation, protection
5115889
5114669


Translation, post-translational modification
5116288
5116031


Translation, post-translational modification
5116623
5116312


Biosynthesis of cofactors, prosthetic group
5116854
5117832


Hypothetical, unclassified, unknown
5122386
5121898


Hypothetical, unclassified, unknown
5122901
5122560


Hypothetical, unclassified, unknown
5125930
5125604


Hypothetical, unclassified, unknown
5135815
5136192


Transcriptional regulators
5155560
5156123


Hypothetical, unclassified, unknown
5162448
5162068


Hypothetical, unclassified, unknown
5168754
5169188


Hypothetical, unclassified, unknown
5169504
5169250


Hypothetical, unclassified, unknown
5174979
5176103


Hypothetical, unclassified, unknown
5197880
5198323


Hypothetical, unclassified, unknown
5204927
5206087


Hypothetical, unclassified, unknown
5206486
5206208


Hypothetical, unclassified, unknown
5207006
5206719


Hypothetical, unclassified, unknown
5210995
5210705


Hypothetical, unclassified, unknown
5212104
5211631


Nucleotide biosynthesis and metabolism
5212832
5213470


Hypothetical, unclassified, unknown
5215669
5216202


Chaperones & heat shock proteins
5216763
5217551


Biosynthesis of cofactors, prosthetic group
5223561
5222539


Cell wall / LPS / capsule
5230910
5230113


Biosynthesis of cofactors, prosthetic group
5231658
5230900


Translation, post-translational modification
5233566
5232484


Translation, post-translational modification
5234852
5233584


Cell wall / LPS / capsule
5236773
5237390


Biosynthesis of cofactors, prosthetic group
5237392
5238240


Nucleotide biosynthesis and metabolism
5238407
5239348


Translation, post-translational modification
5239465
5240079


Translation, post-translational modification
5240121
5240705


Hypothetical, unclassified, unknown
5242558
5242253


Putative enzymes
5246122
5245475


Hypothetical, unclassified, unknown
5248771
5248070


Hypothetical, unclassified, unknown
5250617
5249598


Fatty acid and phospholipid metabolism
5272299
5271484


Amino acid biosynthesis and metabolism
5275731
5274007


Hypothetical, unclassified, unknown
5276282
5276734


Hypothetical, unclassified, unknown
5277171
5276842


Hypothetical, unclassified, unknown
5277950
5277171


Hypothetical, unclassified, unknown
5282158
5282505


Transport of small molecules
5286034
5285267


Hypothetical, unclassified, unknown
5291613
5291960


Hypothetical, unclassified, unknown
5297482
5297006


Biosynthesis of cofactors, prosthetic group
5310725
5311213


Biosynthesis of cofactors, prosthetic group
5311463
5312263


Biosynthesis of cofactors, prosthetic group
5313205
5313585


Energy metabolism
5313675
5315339


Hypothetical, unclassified, unknown
5322234
5322449


Hypothetical, unclassified, unknown
5322706
5322509


Hypothetical, unclassified, unknown
5323100
5322756


Transcription, RNA processing and degr
5325478
5323373


Translation, post-translational modification
5325921
5325652


Translation, post-translational modification
5329948
5327426


Transcription, RNA processing and degra
5331457
5329976


Hypothetical, unclassified, unknown
5331960
5331502


Protein secretion/export apparatus
5332742
5332353


Energy metabolism
5333500
5332745


Cell wall / LPS / capsule
5334903
5333566


Biosynthesis of cofactors, prosthetic rots
5335771
5334920


Cell division
5338522
5337899


Hypothetical, unclassified, unknown
5338617
5338931


Hypothetical, unclassified, unknown
5343754
5343104


Amino acid biosynthesis and metabolism
5345891
5345085


Chaperones & heat shock proteins
5349760
5349200


Transcriptional regulators
5352078
5351674


Transport of small molecules
5352176
5352706


Hypothetical, unclassified, unknown
5353506
5353072


Hypothetical, unclassified, unknown
5361585
5362067


Two-component regulatory systems
5364070
5364735


Transcriptional regulators
5366256
5366654


Hypothetical, unclassified, unknown
5370720
5370475


Hypothetical, unclassified, unknown
5376851
5377708


Hypothetical, unclassified, unknown
5377790
5378095


Hypothetical, unclassified, unknown
5378092
5378841


Hypothetical, unclassified, unknown
5380447
5379512


Related to phage, transposon, or plasmid
5383811
5382795


Hypothetical, unclassified, unknown
5386999
5387721


Energy metabolism
5396858
5395929


Fatty acid and phospholipid metabolism
5402944
5402015


Hypothetical, unclassified, unknown
5414487
5414278


Hypothetical, unclassified, unknown
5418563
5418350


Hypothetical, unclassified, unknown
5419862
5420317


Transcriptional regulators
5422505
5423065


Hypothetical, unclassified, unknown
5434651
5434115


Fatty acid and phospholipid metabolism
5442303
5442773


Fatty acid and phospholipid metabolism
5442791
5444140


Translation, post-translational modification
5445198
5446082


Transcription, RNA processing and degr
5448642
5448965


Transport of small molecules
5460525
5461382


Central intermediary metabolism
5462762
5463604


Hypothetical, unclassified, unknown
5463917
5464435


Central intermediary metabolism
5464820
5466520


Hypothetical, unclassified, unknown
5468282
5468016


Hypothetical, unclassified, unknown
5468408
5469022


Hypothetical, unclassified, unknown
5472041
5471625


Hypothetical, unclassified, unknown
5472438
5472734


Transcriptional regulators
5473765
5474577


Two-component regulatory systems
5480401
5481090


Transport of small molecules
5483767
5482451


Hypothetical, unclassified, unknown
5486355
5486984


Biosynthesis of cofactors, prosthetic group
5487714
5488385


Hypothetical, unclassified, unknown
5489040
5489612


Transcriptional reulators
5490651
5489629


Transcriptional regulators
5505783
5505070


Hypothetical, unclassified, unknown
5507897
5506965


Hypothetical, unclassified, unknown
5517093
5516398


Biosynthesis of cofactors, prosthetic group
5519710
5520537


Hypothetical, unclassified, unknown
5522385
5522972


Hypothetical, unclassified, unknown
5524718
5523867


Hypothetical, unclassified, unknown
5525904
5524969


DNA replication, recombination, modification
5535555
5534161


Translation, post-translational modification
5537288
5537058


Translation, post-translational modification
5537737
5537318


Nucleotide biosynthesis and metabolism
5543364
5542072


Hypothetical, unclassified, unknown
5544820
5544635


Hypothetical, unclassified, unknown
5548644
5548396


Translation, post-translational modification
5549721
5548750


Hypothetical, unclassified, unknown
5553583
5553116


Hypothetical, unclassified, unknown
5556934
5557953


Central intermediary metabolism
5561598
5562413


Hypothetical, unclassified, unknown
5569089
5570627


Hypothetical, unclassified, unknown
5570624
5571160


DNA replication, recombination, modification
5574485
5572221


Hypothetical, unclassified, unknown
5575017
5574493


Hypothetical, unclassified, unknown
5576027
5575014


DNA replication, recombination, modification
5577916
5576027


Hypothetical, unclassified, unknown
5579498
5578680


Hypothetical, unclassified, unknown
5580961
5581707


Putative enzymes
5593423
5592632


Cell wall / LPS / capsule
5605097
5603820


Antibiotic resistance and susceptibility
5606102
5606434


Hypothetical, unclassified, unknown
5606495
5607670


Hypothetical, unclassified, unknown
5607667
5608479


Transport of small molecules
5615543
5613732


Hypothetical, unclassified, unknown
5615651
5616301


Hypothetical, unclassified, unknown
5626378
5624900


Hypothetical, unclassified, unknown
5627133
5626375


Hypothetical, unclassified, unknown
5627864
5627130


Cell wall / LPS / capsule
5628670
5627864


Cell wall / LPS / capsule
5629788
5628667


Cell wall / LPS / capsule
5630852
5629785


Cell wall / LPS / capsule
5631886
5630849


Hypothetical, unclassified, unknown
5659184
5658417


Transcriptional regulators
5662741
5663814


Hypothetical, unclassified, unknown
5663888
5664868


Biosynthesis of cofactors, prosthetic group
5666056
5664989


Amino acid biosynthesis and metabolism
5675701
5675183


Biotility & Attachment
5680712
5679648


DNA replication, recombination, modification
5687495
5689714


Translation, post-translational modification
5689963
5691726


Hypothetical, unclassified, unknown
5691761
5692456


Hypothetical, unclassified, unknown
5702113
5701697


Biosynthesis of cofactors, prosthetic group
5702668
5703438


Hypothetical, unclassified, unknown
5703453
5704079


Hypothetical, unclassified, unknown
5704076
5705677


Amino acid biosynthesis and metabolism
5706190
5706525


Protein secretion/export apparatus
5706551
5706799


Hypothetical, unclassified, unknown
5708035
5708742


Chemotaxis
5708954
5710897


Hypothetical, unclassified, unknown
5720468
5720944


Transcriptional regulators
5723581
5724537


Carbon compound catabolism
5753473
5752463


Central intermediary metabolism
5754143
5753613


Transcriptional regulators
5762149
5762574


Amino acid biosynthesis and metabolism
5766483
5767892


Protein secretion/export apparatus
5777096
5776605


Nucleotide biosynthesis and metabolism
5777387
5777133


Hypothetical, unclassified, unknown
5777808
5777389


Carbon compound catabolism
5778133
5779680


Hypothetical, unclassified, unknown
5779994
5780812


Amino acid biosynthesis and metabolism
5791085
5790444


Hypothetical, unclassified, unknown
5791836
5792234


Hypothetical, unclassified, unknown
5797064
5797336


Transport of small molecules
5802128
5802823


Cell wall / LPS / capsule
5810280
5811338


Cell wall / LPS / capsule
5811335
5812243


Cell wall / LPS / capsule
5812240
5813121


Cell wall LPS / capsule
5813121
5813666


Amino acid biosynthesis and metabolism
5824786
5825718


Hypothetical, unclassified, unknown
5829469
5828903


Hypothetical, unclassified, unknown
5830749
5830312


Hypothetical, unclassified, unknown
5835481
5835894


Putative enzymes
5840894
5839104


Putative enzymes
5843799
5843197


Chaperones & heat shock proteins
5848366
5847971


Putative enzymes
5879970
5878753


Hypothetical, unclassified, unknown
5880481
5879999


Translation, post-translational modification
5883012
5881678


Hypothetical, unclassified, unknown
5883576
5883022


Hypothetical, unclassified, unknown
5883971
5884285


Hypothetical, unclassified, unknown
5885485
5885943


Hypothetical, unclassified, unknown
5896726
5895260


Transcription, RNA processing and degr
5900123
5898864


Energy metabolism
5900694
5900368


Hypothetical, unclassified, unknown
5907389
5907862


Hypothetical, unclassified, unknown
5908329
5907847


Biosynthesis of cofactors, prosthetic group
5921496
5920741


Biosynthesis of cofactors, prosthetic group
5922434
5921493


Hypothetical, unclassified, unknown
5941081
5940746


Cell wall / LPS / capsule
5941335
5941475


Amino acid biosynthesis and metabolism
5942744
5943574


Putative enzymes
5945234
5945932


Central intermediary metabolism
5952820
5952482


DNA replication, recombination, modaficat
5962715
5964724


Energy metabolism
5969764
5969354


Hypothetical, unclassified, unknown
5972202
5971849


Translation, post-translational modificatio
5986118
5985882


DNA replication, recombination, modification
5989319
5988645


DNA replication, recombination, modification
5989459
5990667


Nucleotide biosynthesis and metabolism
5990675
5991130


Hypothetical, unclassified, unknown
5996035
5996985


Energy metabolism
6000142
5999753


Hypothetical, unclassified, unknown
6001377
6000760


Nucleotide biosynthesis and metabolism
6002039
6001398


Hypothetical, unclassified, unknown
6003329
6002958


Transcription, RNA processing and deg
6004095
6003376


Hypothetical, unclassified, unknown
6004276
6005139


Nucleotide biosynthesis and metabolism
6005198
6005809


Hypothetical, unclassified, unknown
6008397
6008777


Hypothetical, unclassified, unknown
6017013
6016621


Carbon compound catabolism
6018996
6018829


Carbon compound catabolism
6019347
6019180


Biosynthesis of cofactors, prosthetic group
6025304
6026194


Two-component regulatory systems
6032267
6031365


Hypothetical, unclassified, unknown
6060199
6059822


Hypothetical, unclassified, unknown
6063831
6063352


Putative enzymes
6069098
6067944


Hypothetical, unclassified, unknown
6074229
6075206


Transcriptional regulators
6082866
6083072


Hypothetical, unclassified, unknown
6083104
6083508


Hypothetical, unclassified, unknown
6083752
6084084


Hypothetical, unclassified, unknown
6084544
6084368


Carbon compound catabolism
6096706
6097026


Hypothetical, unclassified, unknown
6148318
6149181


Hypothetical, unclassified, unknown
6151313
6151525


Hypothetical, unclassified, unknown
6155202
6154783


Hypothetical, unclassified, unknown
6158178
6158942


Translation, post-translational modification
6159562
6158948


Hypothetical, unclassified, unknown
6171732
6171926


Hypothetical, unclassified, unknown
6172872
6172711


Hypothetical, unclassified, unknown
6188854
6188165


Transport of small molecules
6195308
6196315


Hypothetical, unclassified, unknown
6219068
6218856


Transport of small molecules
6221100
6222857


Transport of small molecules
6225924
6224896


Hypothetical, unclassified, unknown
6227081
6227449


Hypothetical, unclassified, unknown
6228243
6227602


Hypothetical, unclassified, unknown
6236228
6235830


Central intermediary metabolism
6244945
6243110


Cell wall / LPS / capsule
6247689
6246325


Energy metabolism
6248235
6247810


Energy metabolism
6249653
6248277


Energy metabolism
6250544
6249684


Energy metabolism
6252139
6250595


Energy metabolism
6252694
6252158


Energy metabolism
6253176
6252706


Energy metabolism
6253491
6253234


Energy metabolism
6254410
6253541


Energy metabolism
6254807
6254427


Cell division
6255843
6254971


Hypothetical, unclassified, unknown
6260053
6259670


Hypothetical, unclassified, unknown
6263563
6261827


Translation, post-translational modification
6264211
6263804


Translation, post-translational modification
6264360
6264226





















TABLE 2









Pa _ID
nt length
prob
Gene Name







4269
4200
0.9999719
rpoC



4270
4074
0.9999719
rpoB



3640
3522
0.9999058
dnaE



1156
2892
0.9995054
nrdA



3834
2853
0.9994519
valS



4560
2832
0.9994208
ileS



595
2775
0.999327
ostA



3168
2772
0.9993217
gyrA



4403
2751
0.9992831
secA



903
2625
0.9990012
alaS



3987
2622
0.9989933
leuS



1787
2610
0.998961
acnB



3011
2607
0.9989528
topA



4744
2523
0.9986937
infB



2615
2436
0.9983575
ftsK



4
2421
0.9982914
gyrB



1803
2397
0.99818
lon



3648
2394
0.9981655



1529
2385
0.9981216
lig



2739
2379
0.9980917
pheT



3704
2310
0.9977116



4964
2265
0.9974239
parC



5050
2220
0.9971
priA



260
2151
0.9965225



1372
2136
0.9963824



2071
2109
0.996116
fusA2



4740
2106
0.9960852
pnp



8
2055
0.9955228
glyS



1532
2046
0.9954155
dnaX



3482
2034
0.9952684
metG



5296
2010
0.9949599
rep



1939
1998
0.9947981



1480
1974
0.9944589
ccmF



5072
1944
0.9940037



2744
1923
0.9936629
thrS



1068
1911
0.9934596



1596
1905
0.9933555
htpG



3157
1890
0.9930879



4967
1890
0.9930879
parE



4044
1884
0.9929779
dxs



1370
1866
0.9926372



3821
1863
0.9925788
secD



3810
1860
0.99252
hscA



1810
1848
0.99228



5549
1836
0.9920322
glmS



4997
1812
0.9915127
msbA



767
1800
0.9912404
lepA



5187
1791
0.9910304



1583
1773
0.9905952
sdhA



5051
1764
0.9903698
argS



5529
1758
0.9902165



3460
1758
0.9902165



4418
1740
0.9897418
ftsl



5568
1737
0.9896605



2298
1725
0.9893287



4696
1725
0.9893287
ilvl



3725
1716
0.9890729
recJ



956
1716
0.9890729
proS



4868
1701
0.9886329
ureC



4526
1701
0.9886329
pilB



3162
1680
0.9879869
rpsA



1794
1671
0.987699
glnS



4732
1665
0.9875032
pgi



2075
1662
0.9874041



2953
1656
0.9872036



4385
1644
0.986793
groEL



3637
1629
0.9862612
pyrG



1251
1626
0.9861522



183
1611
0.9855946
atsA



5065
1602
0.9852493



3769
1578
0.9842875
guaA



2818
1578
0.9842875



3024
1560
0.9835251



5131
1548
0.9829965
pgm



1331
1548
0.9829965



1
1545
0.9828617
dnaA



5556
1545
0.9828617
atpA



4961
1539
0.9825889



3984
1536
0.9824509
lnt



2207
1521
0.9817442



2343
1509
0.9811584
mtlY



3103
1509
0.9811584
xcpR.



1820
1503
0.9808585
nhaB



985
1497
0.9805538



3570
1494
0.9803997
mmsA



4462
1494
0.9803997
rpoN



443
1491
0.9802443



4745
1482
0.9797707
nusA



5006
1479
0.9796104



2097
1476
0.9794487



5237
1467
0.9789561



4417
1464
0.9787893
murE



2037
1461
0.9786211



202
1458
0.9784516



427
1458
0.9784516
oprM



2521
1455
0.9782808
czcB



4483
1455
0.9782808
gatA



4329
1452
0.9781087
pykA



913
1449
0.9779351
mgtE



4484
1446
0.9777602
gatB



4411
1443
0.9775839
murC



1587
1437
0.9772271
lpdG



2073
1431
0.9768646



2002
1425
0.9764964



2391
1425
0.9764964



1551
1416
0.975933



5119
1410
0.9755499
glnA



686
1410
0.9755499



3876
1407
0.9753561
narK2



704
1395
0.9745653



2991
1395
0.9745653
sth



4931
1395
0.9745653
dnaB



3001
1386
0.9739556



1795
1383
0.9737491
cysS



3777
1380
0.973541
xseA



4416
1377
0.9733313
murF



5554
1377
0.9733313
atpD



3746
1374
0.9731199
ffh



2629
1371
0.9729068
purB



373
1368
0.972692
ftsY



1217
1368
0.972692



3081
1368
0.972692



2131
1362
0.9722573



2729
1350
0.9713671



119
1350
0.9713671



4848
1350
0.9713671
accC



4439
1347
0.9711402
trpS



4414
1347
0.9711402
murD



2641
1347
0.9711402
nuoF



2843
1347
0.9711402



2336
1341
0.9706808



4547
1338
0.9704484
pilR



4749
1338
0.9704484
glmM



5224
1335
0.9702141
pepP



2475
1335
0.9702141



3638
1329
0.96974



4243
1329
0.96974
secY



716
1326
0.9695001



2214
1323
0.9692583



2794
1317
0.968769



4887
1317
0.968769



3280
1317
0.968769
oprO



3154
1317
0.968769
wzy



2539
1314
0.9685214



3159
1311
0.9682719
wbpA



2338
1311
0.9682719



1183
1311
0.9682719
dctA



1120
1308
0.9680204



4099
1305
0.9677669



2986
1302
0.9675113



972
1299
0.9672538
tolB



2734
1296
0.9669942



4938
1293
0.9667326
purA



594
1293
0.9667326
surA



3635
1290
0.9664688
eno



1215
1287
0.966203



3977
1284
0.9659351
hemL



2612
1281
0.9656651
serS



4988
1278
0.9653929
waaA



1895
1275
0.9651185



1373
1269
0.9645633
fabF2



4666
1269
0.9645633
hemA



4450
1266
0.9642824
murA



1951
1266
0.9642824



5239
1260
0.9637139
rho



4408
1254
0.9631363
ftsA



2080
1251
0.9628441



2988
1251
0.9628441



1155
1248
0.9625495
nrdB



3147
1242
0.9619534
wbpJ



1488
1239
0.9616518



904
1239
0.9616518
lysC



3153
1236
0.9613478
wzx



3733
1230
0.9607326



1595
1230
0.9607326



2042
1230
0.9607326



1914
1227
0.9604213



2500
1227
0.9604213



446
1224
0.9601075



4008
1224
0.9601075



2928
1224
0.9601075



4566
1221
0.9597913
obg



5221
1218
0.9594726



2347
1218
0.9594726



4212
1218
0.9594726



687
1215
0.9591513



273
1215
0.9591513



1352
1212
0.9588275



1783
1212
0.9588275
nasA



4430
1212
0.9588275



2228
1212
0.9588275



5320
1209
0.9585011
dfp



2219
1209
0.9585011
opdE



1098
1209
0.9585011
fleS



3589
1206
0.9581721



501
1206
0.9581721
bioF



2221
1206
0.9581721



4413
1200
0.9575063
ftsW



1974
1200
0.9575063



4190
1197
0.9571695



1107
1197
0.9571695



2092
1194
0.9568299



2553
1191
0.9564877



1489
1191
0.9564877



3650
1191
0.9564877
dxr



546
1191
0.9564877
metK



4407
1185
0.9557951
ftsZ



4219
1185
0.9557951



2062
1182
0.9554447



2001
1182
0.9554447
atoB



2103
1179
0.9550915



559
1179
0.9550915



4991
1176
0.9547355



3542
1170
0.954015



1896
1170
0.954015



2922
1170
0.954015



1588
1167
0.9536505
sucC



787
1164
0.953283



3891
1164
0.953283



2015
1164
0.953283



552
1164
0.953283
pgk



4636
1161
0.9529127



3773
1158
0.9525394



3523
1158
0.9525394



5390
1155
0.9521632



1237
1152
0.951784



1162
1152
0.951784
dapE



3444
1149
0.9514018



1535
1149
0.9514018



3096
1149
0.9514018
xcpY



3211
1146
0.9510165



1375
1143
0.9506282
pdxB



3800
1143
0.9506282



1509
1143
0.9506282



2940
1140
0.9502368



3806
1140
0.9502368



3643
1137
0.9498423
lpxB



3150
1134
0.9494447
wbpG



2852
1131
0.949044



2626
1128
0.94864
trmU



2552
1128
0.94864



2831
1128
0.94664



4617
1125
0.9482329



4527
1125
0.9482329
pilC



105
1125
0.9482329
coxB



3230
1125
0.9482329



4056
1122
0.9478225
ribD



3149
1122
0.9478225
wbpH



2442
1122
0.9478225
gcvT2



2509
1122
0.9478225
catB



5010
1122
0.9478225
waaG



574
1122
0.9478225



4565
1119
0.9474089
proB



3828
1119
0.9474089



3093
1119
0.9474089



3803
1116
0.946992



689
1113
0.9465718



3117
1113
0.9465718
asd



4002
1104
0.9452911
rodA



2119
1101
0.9448574



146
1098
0.9444202



2167
1098
0.9444202



3701
1096
0.9441269
prfB



4373
1095
0.9439796



4438
1095
0.9439796



643
1092
0.9435355



3969
1086
0.9426368



3167
1086
0.9426368
serC



4665
1083
0.9421821
prfA



4415
1083
0.9421821
mraY



2090
1080
0.9417237



3155
1080
0.9417237
wbpE



1750
1077
0.9412617



2118
1077
0.9412617
ada



5032
1074
0.9407961



4412
1074
0.9407961
murG



5034
1068
0.9398537
hemE



2242
1068
0.9398537



5011
1068
0.9398537
waaC



3827
1068
0.9398537



555
1065
0.9393769
fda



5044
1065
0.9393769
pilM



3148
1065
0.9393769
wbpl



945
1062
0.9388964
purM



3646
1062
0.9388964
lpxD



1004
1059
0.938412
nadA



3360
1059
0.938412



4097
1059
0.938412



69
1059
0.938412



5161
1059
0.938412
rmlB



1777
1053
0.9374317
oprF



646
1053
0.9374317



2963
1050
0.9369357



1690
1050
0.9369357
pscU



3160
1047
0.9364357
wzz



971
1044
0.9359319
tolA



2492
1044
0.9359319
mexT



2549
1044
0.9359319



1409
1041
0.935424
aphA



4149
1041
0.935424



3617
1041
0.935424
recA



5012
1038
0.9349121
waaF



3519
1038
0.9349121



2197
1038
0.9349121



4481
1038
0.9349121
mreB



98
1038
0.9349121



3989
1038
0.9349121
holA



3666
1035
0.9343961
dapD



203
1035
0.9343961



82
1035
0.9343961



3492
1035
0.9343961



5531
1029
0.933519
tonB



580
1026
0.9328235
gcp



4655
1023
0.932291
hemH



3981
1023
0.932291



3759
1023
0.932291



4895
1023
0.932291



2977
1020
0.9317542
murB



4681
1020
0.9317542



4151
1020
0.9317542
acoB



4952
1020
0.9317542



2491
1020
0.9317542



2303
1020
0.9317542



3145
1020
0.9317542
wbpL



2223
1020
0.9317542



3434
1017
0.9312132



1102
1017
0.9312132
fliG



2370
1017
0.9312132



4797
1017
0.9312132



2690
1017
0.9312132



3993
1017
0.9312132



445
1017
0.9312132



2740
1017
0.9312132
pheS



2060
1017
0.9312132



4966
1014
0.930668



3868
1011
0.9301183



5110
1011
0.9301183
fbp



3840
1011
0.9301183



5503
1008
0.9295644



4322
1008
0.9295644



498
1008
0.9295644



4209
1005
0.929006



402
1005
0.929006
pyrB



3195
1005
0.929006
gapA



2026
1002
0.9284432



4238
1002
0.9284432
rpoA



3416
1002
0.9284432



2981
999
0.927876
lpxK



4480
993
0.9267279
mreC



927
990
0.9261471
ldhA



280
990
0.9261471
cysA



143
990
0.9261471



593
987
0.9255616
pdxA



2467
987
0.9255616



2961
987
0.9255616
holB



2253
987
0.9255616
ansA



26
987
0.9255616



728 
984
0.9249716



3996
984
0.9249716
lipA



5033
981
0.9243768



4457
981
0.9243768



5396
978
0.9237773



2227
978
0.9237773



3445
972
0.922564



2854
972
0.922564



4945
972
0.922564
miaA



4569
969
0.9219502
ispB



660
969
0.9219502



543
969
0.9219502



2767
969
0.9219502



4051
969
0.9219502
thiL



3089
966
0.9213315



2293
966
0.9213315



851
963
0.9207078



2683
963
0.9207078



4544
963
0.9207078
rluD



2211
960
0.9200793



1213
960
0.9200793



2975
957
0.9194457
rluC



5085
957
0.9194457



715
957
0.9194457



2051
954
0.9188071



2874
954
0.9188071



815
954
0.9188071



3782
954
0.9188071



407
954
0.9188071
gshB



2730
954
0.9188071



2407
954
0.9188071



3639
951
0.9181635
accA



479
951
0.9181635



3146
951
0.9181635
wbpK



3158
951
0.9181635
wbpB



1911
951
0.9181635



5325
951
0.9181635



9
948
0.9175148
glyQ



2949
948
0.9175148



4557
945
0.9168609
lytB



759
945
0.9168609



829
942
0.9162018



4670
942
0.9162018
prs



2110
942
0.9162018



4420
942
0.9162018



5260
942
0.9162018
hemC



233
942
0.9162018



3242
939
0.9155375



2258
939
0.9155375
ptxR



159
939
0.9155375



2157
939
0.9155375



2968
939
0.9155375
fabD



4561
939
0.9155375
ribF



4926
936
0.914868



4792
936
0.914868



2536
936
0.914868



3036
933
0.9141931



5173
933
0.9141931
arcC



4170
933
0.9141931



2551
933
0.9141931



2507
933
0.9141931
catA



869
933
0.9141931
pbpG



2123
933
0.9141931



4908
933
0.9141931



4068
930
0.9135129



4813
930
0.9135129
lipC



2681
930
0.9135129



2951
930
0.9135129
etfA



4809
930
0.9135129
fdhE



2017
930
0.9135129



3605
927
0.9128273



1517
927
0.9128273



4037
927
0.9128273



1555
927
0.9128273



477
927
0.9128273



3829
924
0.9121363



4174
924
0.9121363



205
921
0.9114397



100
921
0.9114397



2220
921
0.9114397



2383
921
0.9114397



133
918
0.9107377



771
918
0.9107377
era



2469
915
0.9100301 



1986
915
0.9100301
pqqB



113
915
0.9100301



2689
915
0.9100301



70
915
0.9100301



3330
915
0.9100301



2428
915
0.9100301



3850
912
0.9093169



2474
912
0.9093169



4305
912
0.9093169



4406
912
0.9093169
lpxC



3776
909
0.908598



448
909
0.908598



1638
909
0.908598



1342
909
0.908598



5162
909
0.908598
rmlD



3892
909
0.908598



1328
909
0.908598



702
906
0.9078734



1000
906
0.9078734



1145
903
0.9071431



730
903
0.9071431



5364
903
0.9071431



4436
900
0.906407



3886
900
0.906407



932
900
0.906407
cysM



705
900
0.906407



4349
897
0.9056651



1223
894 
0.9049173



2316
894
0.9049173



2877
894
0.9049173



207
894
0.9049173



3433
894
0.9049173



1321
891
0.9041635
cyoE



3312
891
0.9041635



2879
891
0.9041635



5358
891
0.9041635
ubiA



1461
891
0.9041635



2101
891
0.9041635



11
888
0.9034038



1859
888
0.9034038



1589
888
0.9034038
sucD



3088
888
0.9034038



4043
888
0.9034038
ispA



2185
885
0.9026381



4850
885
0.9026381
prmA



5163
882
0.9018663
rmlA



209
882
0.9018663



188
882
0.9018663



1010
879
0.9010883
dapA



2830
876
0.9003042
htpX



412
876
0.9003042
pilK



1138
876
0.9003042



1135
876
0.9003042



2441
876
0.9003042



5562
873
0.8995139
spoOJ



626
873
0.8995139



3112
873
0.8995139
accD



3655
870
0.8987173
tsf



1528
870
0.8987173
zipA



5560
870
0.8987173
atpB



1698
867
0.8979144
popN



2863
867
0.8979144
lipH



2915
867
0.8979144



1630
867
0.8979144



5335
864
0.8971052



5457
864
0.8971052



4409
864
0.8971052
ftsQ



211
864
0.8971052
mdcD



5555
861
0.8962895
atpG



1622
861
0.8962895



2418
861
0.8962895



2142
861
0.8962895



1687
861
0.8962895
speE



4861
858
0.8954674



4788
858
0.8954674



3292
858
0.8954674



2294
855
0.8946387



244
855
0.8946387



708
855
0.8946387



1796
855
0.8946387
folD



376
855
0.8946387
rpoH



768
855
0.8946387
lepB



3185
852
0.8938035



4314
852
0.8938035
purU1



4750
852
0.8938035
folP



4925
852
0.8938035



1496
852
0.8938035



4669
849
0.8929616
ipk



1539
849
0.8929616



2088
849
0.8929616



4524
849
0.8929616
nadC



3787
849
0.8929616



2095
846
0.8921131



3836
846
0.8921131
kdsA



1364
843
0.8912579



4864
843
0.8912579
ureD



1454
843
0.8912579



184
840
0.8903958



4215
837
0.889527



3384
837
0.889527
phnC



2329
837
0.889527



3315
834
0.8886512



1379
834
0.8886512



5278
831
0.8877685
dapF



4296
828
0.8868789



978
828
0.8868789



4920
828
0.8868789
nadE



3395
828
0.8868789
nosY



503
825
0.8859821



1619
825
0.8859821



4552
825
0.8859821
pilW



3348
825
0.8859821



1938
822
0.8850783



4260
822
0.8850783
rplB



2251
819
0.8841673



4167
819
0.8841673



3936
819
0.8841673



4969
819
0.8841673



5132
819
0.8841673



238
816
0.883249



3651
816
0.883249
cdsA



4693
816
0.883249
pssA



187
816
0.883249



4956
816
0.883249
rhdA



790
816
0.883249



1164
813
0.8823235



820
813
0.8823235



2074
813
0.8823235



4992
813
0.8823235



4878
813
0.8823235



204
810
0.8813907



4492
810
0.8813907



2591
607
0.8804504



1624
807
0.8804504



4759
807
0.8804504
dapB



3022
807
0.8804504



5009
807
0.8804504
waaP



35
807
0.8804504
trpA



3314
804
0.8795027



3505
804
0.8795027



2678
804
0.8795027



2010
804
0.8795027



1732
801
0.8785475



341
801
0.8785475
lgt



4729
801
0.8785475
panB



4662
798
0.8775847
murI



550
798
0.8775847



4455
798
0.8775847



2295
798
0.8775847



2013
798
0.8775847



416
795
0.8766143



2349
795
0.8766143



342
795
0.8766143
thyA



1872
792
0.8756362



3353
792
0.8756362



4980
792
0.8756362



1691
789
0.8746503
pscT



642
789
0.8746503



4651
789
0.8746503



4157
789
0.8746503



1462
789
0.8746503



3443
789
0.8746503



3578
786
0.8736566



3657
786
0.8736566
map



4348
786
0.8736566



2260
783
0.8726551



862
783
0.8726551



236
780
0.8716456



2811
780
0.8716456



1224
780
0.8716456



4122
780
0.8716456



4699
780
0.8716456



3644
777
0.8706281
lpxA



3397
777
0.8706281
fpr



3512
777
0.8706281



1307
774
0.8696025



4330
774
0.8696025



3609
771
0.8685688
potC



5063
771
0.8685688
ubiE



1366
771
0.8685688



611
771
0.8685688
prtR



639
771
0.8685688



4341
771
0.8685688



2839
771
0.8685688



2234
771
0.8685688



4706
768
0.8675269



1897
768
0.8675269



2554
768
0.8675269



5028
768
0.8675269



2979
765
0.8664768
kdsB



216
765
0.8664768



5469
765
0.8664768



3220
765
0.8664768



2411
765
0.8664768



1591
765
0.8664768



2989
765
0.8664768



1088
762
0.8654183



2515
762
0.8654183
xylL



1021
762
0.8654183



4663
759
0.8643515
moeB



4389
759
0.8643515



1012
759
0.8643515



1477
759
0.8643515
ccmC



5007
759
0.8643515



3743
759
0.8643515
trmD



3805
759
0.8643515
pilF



3151
756
0.8632761
hisF2



4350
756
0.8632761



4748
756
0.8632761
tpiA



5259
756
0.8632761
hemD



3652
756
0.8632761
uppS



339
756
0.8632761



1125
753
0.8621923



3851
753
0.8621923



1369
753
0.8621923



1952
753
0.8621923



182
753
0.8621923



309
753
0.8621923



2952
750
0.8610999
etfB



4790
750
0.8610999



1350
750
0.8610999



4049
747
0.8599988



1216
747
0.8599988



4972
747
0.8599988



4279
747
0.8599988



2967
744
0.8588889
fabG



2803
744
0.8588889



544
744
0.8588889



4083
741
0.8577703



1816
741
0.8577703
dnaQ



3656
741
0.8577703
rpsB



4299
738
0.8566428



1892
738
0.8566428



3004
738
0.8566428



3654
738
0.8566428
pyrH



4388
735
0.8555064



3671
735
0.8555064



5008
735
0.8555064



1559
732
0.854361



1733
732
0.854361



1165
729
0.8632064



2224
729
0.8532064



3317
729
0.8532064



3477
726
0.8520428
rhlR



489
726
0.8520428



4461
726
0.8520428



1792
723
0.8508699



3494
723
0.8508699



4802
723
0.8508699



502
723
0.8508699



3888
723
0.8508699



4181
720
0.8496877



2229
720
0.8496877



5334
720
0.8496877
rph



531
717
0.8484961



3857
717
0.8484961



3249
717
0.8484961



3606
717
0.8484961



906
714
0.8472951



2749
714
0.8472951
endA



4906
714
0.8472951



2544
714
0.8472951



1106
714
0.8472951



993
714
0.8472951



1157
711
0.8460846



1013
711
0.8460846
purC



1584
708
0.8448844
sdhB



1348
708
0.8448644



5071
708
0.8448644



58
705
0.8436346



947
705
0.8436346



3633
705
0.8436346



2800
705
0.8436346



4064
705
0.8436346



1475
702
0.8423951
ccmA



1371
702
0.8423951



4679
702
0.8423951



279
699
0.8411457



3171
699
0.8411457
ubiG



5281
699
0.8411457



2876
699
0.8411457
pyrF



3488
699
0.8411457



3681
696
0.8398864



4273
696
0.8398864
rplA



3731
696
0.8398864



5154
696
0.8398864



4916
696
0.8398864



2105
696
0.8398864



5052
696
0.8398864



969
696
0.8398864
tolQ



1894
693
0.8386172



2280
693
0.8386172



213
693
0.8386172



733
693
0.8386172



3163
690
0.8373379
cmk



5496
690
0.8373379



4885
690
0.8373379
irlR



4257
687
0.8360484
rpsC



2719
687
0.8360484



120
687
0.8360484



504
687
0.8360484
bioD



1862
687
0.8360484
modB



527
684
0.8347487
dnr



1118
684
0.8347487



2987
684
0.8347487



2617
681
0.8334387
aat



3685
681
0.8334387



2638
678
0.8321183
nuoB



1980
678
0.8321183



2034
675
0.8307875



1261
675
0.8307875



2996
675
0.8307875
nqrD



3528
675
0.8307875
rnt



453
675
0.8307875



976
675
0.8307875



5319
675
0.8307875
radC



607
675
0.8307875
rpe



2284
672
0.8294461



1167
672
0.8294461



1476
672
0.8294461
ccmB



1193
672
0.8294461



4892
672
0.8294461
ureF



330
672
0.8294461
rpiA



944
669
0.8280941
purN



1269
669
0.8280941



243
669
0.8280941



167
666
0.8287314



65
666
0.8267314



4029
666
0.8267314



3368
666
0.8267314



1978
666
0.8267314



4776
666
0.8267314



1623
663
0.8253578



3181
663
0.8253578



3890
663
0.8253578



1090
663
0.8253578



697
663
0.8253578



1526
660
0.8239734



2782
660
0.8239734



3110
660
0.8239734



4055
660
0.8239734
ribC



4121
660
0.8239734



2832
657
0.822578
tpm



2351
654
0.8211715



3550
651
0.8197539
algF



4998
651
0.8197539



4757
651
0.8197539



1504
651
0.8197539



1049
648
0.818325
pdxH



655
648
0.818325



2222
648
0.818325



3859
648
0.818325



2257
648
0.818325
pvcD



3973
648
0.818325



4676
648
0.818325



4453
648
0.818325



1905
648
0.818325



4216
645
0.8168848



4006
645
0.8168848



2473
645
0.8168848



1825
645
0.8168848



652
645
0.8168848
vfr



251
642
0.8154332



5331
642
0.8154332
pyrE



5142
642
0.8154332
hisH1



5534
642
0.8154332



3730
642
0.8154332



2007
639
0.8139701
maiA



2726
639
0.8139701



2720
639
0.8139701



4646
639
0.8139701
upp



826
639
0.8139701



3495
639
0.8139701
nth



3678
639
0.8139701



3450
639
0.8139701



2066
639
0.8139701



990
639
0.8139701



4182
639
0.8139701



2983
636
0.8124954



3246
636
0.8124954
rluA



114
636
0.8124954



4263
636
0.8124954
rplC



2126
636
0.8124954



4507
633
0.811009



1558
633
0.811009



1397
633
0.811009



2962
633
0.811009
tmk



4890
630
0.8095108



629
630
0.8095108



4019
630
0.8095108



4440
630
0.8095108



3232
627
0.8080008



2614
627
0.8080008
lolA



5064
627
0.8080008



853
624
0.8064788



3665
624
0.8064788



1790
624
0.8064788



4752
624
0.8064788
ftsJ



981
624
0.8064788



3988
624
0.8064788



5341
621
0.8049447



4239
621
0.8049447
rpsD



1757
618
0.8033984
thrH



2504
618
0.8033984



4668
618
0.8033984



4428
618
0.8033984
sspA



5330
618
0.8033984



4047
618
0.8033984
ribA



2807
618
0.8033984



3407
618
0.8033984
hasAp



1315
615
0.8018399



5470
615
0.8018399



4671
615
0.8018399



1219
615
0.8018399



571
615
0.8018399



4871
615
0.8018399



3754
612
0.800269



3354
612
0.800269



4529
612
0.800269



5336
612
0.800269
gmk



3152
609
0.7986857
hisH2



1962
609
0.7986857



2459
606
0.7970898



154
606
0.7970898
pcaG



2602
606
0.7970898



1432
606
0.7970898
lasI



3326
606
0.7970898



377
606
0.7970898



4262
603
0.7954813
rplD



1089
603
0.7954813



5190
603
0.7954813



3273
600
0.7938601



2451
600
0.7938601



3472
597
0.7922259



370
597
0.7922259



3030
597
0.7922259



2792
597
0.7922259



1172
597
0.7922259
napC



3446
594
0.7905789



4012
594
0.7905789



2916
594
0.7905789



4425
594
0.7905789



684
594
0.7905789



4345
591
0.7889187



4063
591
0.7889187



3281
591
0.7889187



3796
588
0.7872454



2774
588
0.7872454



4553
588
0.7872454
pilX



4923
588
0.7872454



763
585
0.7855589
mucA



2196
585
0.7855589



3765
585
0.7855589



1847
585
0.7855589



3489
585
0.7855589



3414
585
0.7855589



4672
585
0.7855589



1280
585
0.7855589



4366
582
0.7838589
sodB



2936
582
0.7838589



3255
579
0.7821455



1785
579
0.7821455



111
579
0.7821455



358
579
0.7821455



3867
576
0.7804185



3156
576
0.7804185
wbpD



776
573
0.7786779



3784
573
0.7786779



4894
573
0.7786779



4459
573
0.7786779



2372
573
0.7786779



2910
570
0.7769234



1928
570
0.7769234
rimJ



475
570
0.7769234



1955
570
0.7769234



422
570
0.7769234



405
570
0.7769234



2851
567
0.775155
efp



5176
567
0.775155



1994
564
0.7733726



4600
564
0.7733726
nfxB



4499
564
0.7733726



4171
564
0.7733726



139
564
0.7733726
ahpC



3227
564
0.7733726
ppiA



1427
564
0.7733726



2331
561
0.7715761



2406
561
0.7715761



3438
561
0.7715761
folE1



4831
561
0.7715761



4762
561
0.7715761
grpE



2584
561
0.7715761
pgsA



1204
558
0.7697653



1675
558
0.7697653



3653
558
0.7697653
frr



22
558
0.7697653



2784
558
0.7697653



3291
555
0.7679402



5225
555
0.7679402



535
555
0.7679402



1472
555
0.7679402



311
555
0.7679402



2743
552
0.7661006
infC



1635
552
0.7661006
kdpC



1884
552
0.7661006



54
549
0.7642464



3767
549
0.7642464



1543
549
0.7642464
apt



2365
546
0.7623775



5164
546
0.7623775
rmlC



2434
546
0.7623775



149
546
0.7623775



1674
546
0.7623775
folE2



171
543
0.7604938



1481
543
0.7604938
ccmG



3726
540
0.7585952



4251
540
0.7585952
rplE



1768
540
0.7585952



937
540
0.7585952



6
537
0.7566615



5557
537
0.7566815
atpH



3396
537
0.7566815
nosL



4841
537
0.7566815



2971
537
0.7566815



4962
537
0.7566815



4248
534
0.7547527
rplF



1377
534
0.7547527



1885
534
0.7547527



4275
534
0.7547527
nusG



4649
534
0.7547527



2985
534
0.7547527



1154
534
0.7547527



5111
531
0.7528085
gloA3



4765
531
0.7528085
omlA



3575
531
0.7528085



4031
528
0.750849
ppa



1300
528
0.750849



2733
528
0.750849



4460
528
0.750849



3905
528
0.750849



3744
528
0.750849
rimM



1867
528
0.750849



2455
528
0.750849



514
525
0.7488739
nirL



4965
525
0.7488739



2464
525
0.7488739



3095
525
0.7488739
xcpZ



2136
525
0.7488739



1134
522
0.7468831



1062
522
0.7468831



1442
522
0.7468831



3693
522
0.7468831



3811
522
0.7468831
hscB



145
519
0.7448766



1845
519
0.7448766



3100
519
0.7448766
xcpU



4866
519
0.7448766



5039
519
0.7448766
arok



2496
516
0.7428542



3911
516
0.7428542



4050
516
0.7428542
pgpA



1610
516
0.7428542
fabA



3287
516
0.7428542



403
513
0.7408157
pyrR 



1514
510
0.7387611



4114
510
0.7387611



4559
510
0.7387611
lspA



47
510
0.7387611



4104
510
0.7387611



3965
510
0.7387611



2184
510
0.7387611



1912
507
0.7366902



1657
507
0.7366902



1666
507
0.7366902



55
507
0.7366902



3647
507
0.7366902



973
507
0.7366902



585
507
0.7366902



2859
507
0.7366902
greB



350
507
0.7366902
folA



3288
504
0.7346029



1967
501
0.732499



4272
501
0.732499
rplJ



4246
501
0.732499
rpsE



3318
501
0.732499



3756
501
0.732499



2226
501
0.732499



2645
501
0.7324991
nuoJ



2367
498
0.7303785



1837
498
0.7303785



261
498
0.7303785



4232
498
0.7303785
ssb



1035
495
0.7282411



5128
492
0.7260868
secB



1173
492
0.7260868
napB



1176
492
0.7260868
napF



1772
489
0.7239154



4211
489
0.7239154



1900
489
0.7239154



1899
489
0.7239154



1745
489
0.7239154



1956
489
0.7239154



4210
489
0.7239154



4574
489
0.7239154



2517
489
0.7239154
xylY



4728
489
0.7239154
folK



3403
486
0.7217268



837
486
0.7217268
slyD



2768
483
0.7195209



3856
483
0.7195209



4295
483
0.7195209



2797
483
0.7195209



3918
483
0.7195209
moaC



3982
483
0.7195209



4773
483
0.7195209



5247
483
0.7195209



5222
483
0.7195209



5385
480
0.7172975



4052
480
0.7172975
nusB



363
480
0.7172975
coaD



2935
480
0.7172975



2461
480
0.7172975



2819
480
0.7172975



2721
480
0.7172975



698
480
0.7172975



336
480
0.7172975



4395
480
0.7172975



3207
480
0.7172975



1464
480
0.7172975



1026
477
0.7150564



714
477
0.7150564



2205
477
0.7150564



4053
477
0.7150564
ribE



5081
477
0.7150564



3785
477
0.7150564



1696
477
0.7150564
pscO



1924
477
0.7150564



4718
477
0.7150564



808
474
0.7127976



4644
474
0.7127976



1593
474
0.7127976



5246
474
0.7127976



4454
474
0.7127976



1008
474
0.7127976
bcp



1039
474
0.7127976



116
474
0.7127976



1206
474
0.7127976



3627
474
0.7127976



3302
471
0.7105208



5558
471
0.7105208
atpF



4267
471
0.7105208
rpsG 



2052
471
0.7105208
cynS



4847
471
0.7105208
accB



962
471
0.7105208



2171
471
0.7105208



4948
468
0.7082261



332
468
0.7082261



4107
468
0.7082261



1482
468
0.7082261
ccmH



4183
468
0.7082261



2427
468
0.7082261



2786
468
0.7082261



953
465
0.7059131



4564
465
0.7059131



2731
465
0.7059131



4464
465
0.7059131
ptsN



80
465
0.7059131



4057
465
0.7059131



2978
465
0.7059131
ptpA



1306
462
0.7035818



3616
462
0.7035818



1673
462
0.7035818



3470
459
0.701232



3380
459
0.701232



4746
459
0.701232



5229
459
0.701232



3320
456
0.6988636



2499
456
0.6988636



3309
456
0.6988636



4828
456
0.6988636



59
456
0.6988636
osmC



5321
456
0.6988636
dut



4421
456
0.6988636



4697
453
0.6964764



2538
453
0.6964764



2829
453
0.6964764



3916
453
0.6964764
moaE



3435
453
0.6964764



115
453
0.6964764



578
450
0.6940703



678
450
0.6940703



4525
450
0.6940703
pilA



1285
450
0.6940703



614
450
0.6940703



822
447
0.6916451



245
447
0.6916451
aroQ2



1815
447
0.6916451
rnhA



1594
447
0.6916451



4630
444
0.6892007



1122
444
0.6892007



3067
444
0.6892007



1105
444
0.6892007
fliJ



970
441
0.6867369
tolR



2982
441
0.6867369



3645
441
0.6867369
fabZ



61
438
0.6842536



1835
438
0.6842536



5178
438
0.6842536



1618
438
0.6842536



2577
438
0.6842536



3017
438
0.6842536



2775
438
0.6842538



1710
438
0.6842536
exsC



3341
435
0.6817506



94
435
0.6817506



2436
435
0.6817506



4244
435
0.6817506
rplO



2756
435
0.6817506



404
435
0.6817506



4610
435
0.6817506



250
435
0.6817506



4767
435
0.6817506



433
435
0.6817506



2675
435
0.6817506



720
435
0.6817506



679
432
0.6792278



3807
432
0.6792278
ndk



4274
432
0.6792278
rplK



3986
432
0.6792278



52
429
0.6766849



4433
429
0.6766849
rplM



1560
429
0.6766849



2282
429
0.6766849



2120
429
0.6766849



4169
429
0.6766849



5116
426
0.6741219



2368
426
0.6741219



2673
426
0.6741219



700
426
0.6741219



5553
426
0.6741219
atpC



2187
426
0.6741219



3332
426
0.6741219



45181
426
0.6741219



2894
423
0.6715386



653
423
0.6715386



661
423
0.6715386



542
420
0.6689348



5130
420
0.6689348



5465
420
0.6689348



4935
420
0.6689348
rpsF



850
420
0.6689348



2225
417
0.6663104



4874
417
0.6663104



5061
417
0.6663104



1468
417
0.6663104



264
417
0.6663104



3962
417
0.6663104



868
414
0.6636651



5182
414
0.6636651



1353
414
0.6636651



2192
414
0.6636651



3289
414
0.6636651



4256
414
0.6636651
rplP



3558
414
0.6636651



2674
411
0.6609989



3611
411
0.6609989



5300
411
0.6609989
cycB



2769
411
0.6609989



3960
408
0.6583116



1203
408
0.6583116



5569
408
0.6583116
rnpA



4427
408
0.6583116
sspB



1129
408
0.6583116



1465
408
0.6583116



1645
408
0.6583116



1659
408
0.6583116



4764
405
0.6556029
fur



778
405
0.6556029



474
405
0.6556029



5404
405
0.6558029



398
405
0.6556029



2016
405
0.6556029



1883
399
0.650121



5144
399
0.650121



2827
399
0.650121



2107
399
0.650121



5543
399
0.650121



3674
399
0.650121



4778
399
0.650121



1358
399
0.650121



2706
396
0.6473475



1250
396
0.6473475
aprI



710
396
0.6473475
gloA2



3788
396
0.6473475



42
396
0.6473475



2375
396
0.6473475



5195
396
0.6473475



4405
396
0.6473475



2605
396
0.6473475



3904
396
0.6473475



4471
396
0.6473475



4249
393
0.6445519
rpsH



5347
393
0.6445519



4125
393
0.6445519
hpcD



4432
393
0.6445519
rpsI



3967
393
0.6445519



2722
393
0.6445519



5328
390
0.6417342



4240
390
0.6417342
rpsK



4237
390
0.6417342
rplQ



4747
390
0.6417342
secG



1817
390
0.6417342



3432
390
0.6417342



3884
387
0.6388941



3813
387
0.6388941
iscU



1581
387
0.6388941
sdhC



540
387
0.8388941



3021
387
0.6388941



4383
384
0.6360315



4392
384
0.6360315



2446
384
0.6360315
gcvH2



5566
384
0.6360315



3869
384
0.6360315



1160
384
0.6360315



3906
384
0.6360315



867
384
0.6360315



4731
381
0.6331462
panD



1355
381
0.6331462



3041
381
0.6331462



5339
381
0.6331462



880
381
0.6331462



1095
381
0.6331462



561
381
0.6331462
atpI



591
381
0.6331462



1518
381
0.6331462



170
381
0.6331462



4603
381
0.6331462



3123
378
0.6302381



4424
378
0.6302381



4586
378
0.6302381



3178
378
0.6302381



991
378
0.6302381



4059
378
0.6302381



4485
378
0.6302381



5381
378
0.6302381



908
375
0.6273069



2490
375
0.6273069



680
375
0.6273069



2753
375
0.6273069



1456
375
0.6273069
cheY



3012
375
0.6273069



4076
375
0.6273069



4315
375
0.6273069
mvaT



3439
372
0.6243525
folX



4268
372
0.6243525
rpsL



5333
372
0.6243525



2898
369
0.6213746



5533
369
0.6213746



1541
369
0.6213746



4253
369
0.6213746
rplN



3833
369
0.6213746



1149
369
0.6213746



4271
369
0.6213746
rplL



4276
369
0.6213746
secE



1582
369
0.6213746
sdhD



2166
366
0.6183732



33
366
0.6183732



1701
366
0.6183732



1842
363
0.6153479



1378
363
0.6153479



3203
363
0.6153479



1840
363
0.6153479



3843
363
0.6153479



1076
363
0.6153479



630
363
0.6153479



613
360
0.6122987



2901
360
0.6122987



2606
360
0.6122987



4324
360
0.6122987



2868
360
0.6122987



1492
357
0.6092253



4005
357
0.6092253



2741
357
0.6092253
rplT



2666
357
0.6092253



1426
357
0.6092253



4241
357
0.6092253
rpsM



2960
357
0.6092253
pilZ



871
357
0.6092253
phhB



1995
357
0.6092253



2667
354
0.6061275



5303
354
0.6061275



582
354
0.6061275
folB



1568
354
0.6061275



2736
354
0.6061275



563
354
0.6061275



1349
351
0.6030052



665
351
0.6030052



4247
351
0.6030052
rplR



320
351
0.6030052



3742
351
0.6030052
rplS



3835
351
0.6030052



1228
351
0.6030052



2175
348
0.5998581



729
348
0.5998581



570
348
0.5998581



1720
348
0.5998581
pscG



4711
348
0.5998581



3684
348
0.5998581



4702
348
0.5998581



3664
348
0.5998581



1917
348
0.5998581



2190
345
0.5966861



2762
345
0.5966861



3688
345
0.5966861



2780
345
0.5966861



3046
345
0.5966861



4739
345
0.5966861



1398
342
0.5934889



128
342
0.5934889



4575
342
0.5934889



2456
342
0.5934889



2781
342
0.5934889



2715
339
0.5902664



5288
339
0.5902664
glnK



3809
339
0.5902664
fdx2



3822
339
0.5902664



1055
339
0.5902664



1722
339
0.5902664
pscI



3367
339
0.5902664



565
339
0.5902664



2608
336
0.5870183



1965
336
0.5870183



644
336
0.5870183



825
336
0.5870183



1114
336
0.5870183



5275
336
0.5870183



5067
336
0.5870183
hisE



589
333
0.5837445



4258
333
0.5837445
rplV



4990
333
0.5837445



1323
333
0.5837445



5406
333
0.5837445



3979
333
0.5837445



3140
330
0.5804447



2405
330
0.5804447



1540
330
0.5804447



3275
330
0.5804447



4698
330
0.5804447



1702
330
0.5804447



3040
330
0.5804447



939
327
0.5771188



1925
327
0.5771188



1780
327
0.5771188
nirD 



4577
327
0.5771188



3533
327
0.5771188



2694
327
0.5771188



5240
327
0.5771188
trxA



617
327
0.5771188



1533
327
0.5771188



4164
327
0.5771188



1882
324
0.5737665



3351
324
0.5737665



894
324
0.5737665



3042
324
0.5737665



1362
324
0.5737665



3812
324
0.5737665
iscA



802
324
0.5737665



4853
324
0.5737665
fis



2384
324
0.5737665



488
321
0.5703877



1123
321
0.5703877



1676
321
0.5703877



1168
321
0.5703877



5417
321
0.5703877
soxD



3502
318
0.566982



1038
318
0.566982



15
318
0.566982



2422
315
0.5635494



3854
315
0.5635494



610
315
0.5635494
prtN



4252
315
0.5635494
rplX



2658
315
0.5635494



1830
315
0.5635494



4753
315
0.5635494



922
315
0.5635494



2759
315
0.5635494



5227
315
0.5635494



4264
312
0.5600895
rpsJ



3260
312
0.5600895



4568
312
0.5600895
rplU



742
309
0.5566022



2937
309
0.5566022



2646
309
0.5566022
nuoK



979
309
0.5566022



4463
309
0.5566022



4452
309
0.5566022



2174
309
0.5566022



1937
309
0.5566022



786
306
0.5530873



3142
306
0.5530873



4674
306
0.5530873



3347
306
0.5530873



2161
306
0.5530873



4230
306
0.5530873
pchB



2245
306
0.5530873



4789
306
0.5530873



4250
306
0.5530873
rpsN



2607
306
0.5530873



857
306
0.5530873
bolA



466
303
0.5495445



3390
303
0.5495445



647
303
0.5495445



3298
303
0.5495445



2738
303
0.5495445
himA



4354
303
0.5495445



3278
300
0.5459736



4261
300
0.5459736
rplW



2029
300
0.5459736



4141
300
0.5459736



3202
300
0.5459736



2799
300
0.5459736



2460
297
0.5423744



1929
297
0.5423744



709
297
0.5423744



4875
297
0.5423744



1705
297
0.5423744
pcrG



3662
294
0.5387467



4419
294
0.5387467
ftsL



4386
294
0.5387467
groES



3566
294
0.5387467



1295
294
0.5387467



490
294
0.5387467



900
291
0.5350903



4482
291
0.5350903
gatC



369
291
0.5350903



4642
291
0.5350903



3338
291
0.5350903



4638
288
0.5314048



2143
288
0.5314048



983
288
0.5314048



131
288
0.5314048



3274
288
0.5314048



980
285
0.5276901



3634
285
0.5276901



3161
285
0.5276901
himD



4298
285
0.5276901



2183
285
0.5276901



3998
282
0.523946



3051
282
0.523946



124
282
0.523946



2292
282
0.523946



3940
282
0.523946



4176
282
0.523946
ppiC2



2697
282
0.523946



1641
279
0.5201722



3033
279
0.5201722



1988
279
0.5201722
pqqD



1996
279
0.5201722
ppiC1



2485
279
0.5201722



4060
279
0.5201722



2723
279
0.5201722



4637
279
0.5201722



4018
276
0.5163685



4563
276
0.5163685
rpsT



909
276
0.5163685



4259
276
0.5163685
rpsS



68
276
0.5163685



954
276
0.5163685



1852
276
0.5163685



1298
276
0.5163685



5148
273
0.5125346



734
273
0.5125346



4466
273
0.5125346



2487
273
0.5125346



818
273
0.5125346



2182
270
0.5086704



1447
270
0.5086704
fliQ



4033
270
0.5086704



4741
270
0.5086704
rpsO



4870
267
0.5047755



3413
267
0.5047755



4254
267
0.5047755
rpsQ



874
267
0.5047755



1963
267
0.5047755



2805
264
0.5008497



3601
264
0.5008497



3085
264
0.5008497



986
264
0.5008497



1151
264
0.5008497
imm2



1508
261
0.4968928



712
258
0.4929045



1968
258
0.4929045



2663
258
0.4929045



1719
258
0.4929045
pscF



5559
258
0.4929045
atpE



1233
258
0.4929045



384
258
0.4929045



4567
258
0.4929045
rpmA



2737
258
0.4929045



635
255
0.4888847



5129
255
0.4888847
grx



1394
255
0.4888847



4611
255
0.4888847



53
255
0.4888847



2031
255
0.4888847



3245
255
0.4888847
minE



3917
252
0.4848329
moaD



2853
252
0.4848329
oprI



1063
252
0.4848329



3745
252
0.4848329
rpsP



362
252
0.4848329
fdx1



1006
252
0.4848329



4944
249
0.4807491



493
249
0.4807491



5068
249
0.4807491
tatA 



3632
249
0.4807491



4782
246
0.4766328



2429
246
0.4766328



1711
246
0.4766328



2297
246
0.4766328



738
246
0.4766328



4134
243
0.472484



4377
243
0.472484



1431
243
0.472484
rsaL



4357
243
0.472484



2149
243
0.472484



1849
243
0.472484



1869
240
0.4683022



1564
240
0.4683022



3334
240
0.4683022



1743
240
0.4683022



2621
237
0.4640873



1592
237
0.4640873



5316
237
0.4640873
rpmB



2966
237
0.4640873
acpP



2845
234
0.4598397



3009
234
0.459839



60
234
0.459839



2703
234
0.459839



505
231
0.455557



4934
231
0.455557
rpsR



648
231
0.455557



632
231
0.455557



1404
228
0.451241



805
228
0.451241



125
228
0.451241



39
228
0.451241



2992
226
0.451241



4359
228
0.451241



2021
225
0.4468909



3530
222
0.4425063



2453
222
0.4425063



1855
222
0.4425063



3612
222
0.4425063



3031
222
0.4425063



4028
222
0.4425063



3237
222
0.4425063



2785
219
0.4380869



3501
219
0.4380869



2412
219
0.4380869



2619
219
0.4380869
infA



4306
219
0.4380869



4826
219
0.4380869



38
216
0.4336324



4737
216
0.4336324



579
216
0.4336324
rpsU



717
213
0.4291427



3049
213
0.4291427
rmf



5526
213
0.4291427



5460
213
0.4291427



200
213
0.4291427



2763
210
0.4246174



2170
210
0.4246174



456
210
0.4246174



4823
210
0.4246174



109
210
0.4246174



960
210
0.4246174



2668
210
0.4246174




1159
210
0.4246174



3266
210
0.4246174
capB



3451
210
0.4246174



627
207
0.4200562



5403
207
0.4200562



4077
207
0.4200562



1718
204
0.4154588
pscE



4530
201
0.410825



380
201
0.410825



553
201
0.410825



3808
201
0.410825



4738
198
0.4061544



1230
198
0.4061544



3520
195
0.4014469



3752
195
0.4014469



5480
195
0.4014469



2742
195
0.4014469
rpmI



2808
192
0.396702



4255
192
0.396702
rpmC



1747
189
0.3919195



905
186
0.3870991
csrA



3371
186
0.3870991



258
186
0.3870991



2980
186
0.3870991



4940
186
0.3870991



284
183
0.3822405



2970
183
0.3822405
rpmF



1571
180
0.3773433



3496
180
0.3773433



1478
177
0.3724074



5408
177
0.3724074



3572
177
0.3724074



4245
177
0.3724074
rpmD



2186
171
0.3624178



4537
171
0.3624178



2501
168
0.3573635



2883
168
0.3573635



1177
168
0.3573635
napE



5351
168
0.3573635



5350
168
0.3573635



2146
168
0.3573635



3719
162
0.3471344



5482
162
0.3471344



2311
159
0.341959



587
159
0.341959



161
153
0.3314847



3600
153
0.3314847



3990
153
0.3314847



3370
147
0.3208437



135
141
0.3100333



5276
141
0.3100333
lppL



1664
141
0.3100333



5570
135
0.2990509
rpmH



3144
120
0.2708239



442
117
0.2650435



4242
117
0.2650435
rpmJ



1632
90
0.210914
kdpF



1985
72
0.1726306
pqqA











Protein Name










DNA-directed RNA polymerase beta* chain


DNA-directed RNA polymerase beta chain


DNA polymerase III, alpha chain


ribonucleoside reductase, large chain


valyl-tRNA synthetase


isoleucyl-tRNA synthetase


organic solvent tolerance protein OstA precursor


DNA gyrase subunit A


secretion protein SecA


alanyl-tRNA synthetase


leucyl-tRNA synthetase


aconitate hydratase 2


DNA topoisomerase I


translation initiation factor IF-2


cell division protein FtsK


DNA gyrase subunit B


Lon protease


probable outer membrane protein


DNA ligase


phenylalanyl-tRNA synthetase, beta subunit


probable chemotaxis sensor/effector fusion protein


topoisomerase IV subunit A


primosomal protein N′


hypothetical protein


hypothetical protein


elogation factor G


polyribonucleotide nucleotidyltransferase


glycyl-tRNA synetase beta chain


DNA polymerase subunits gamma and tau


methionyl-tRNA synthetase


ATP-dependent DNA helicase Rep


hypothetical protein


cytochrome C-type biogenesis protein CcmF


probable chemotaxis transducer


threonyl-tRNA synthetase


probable heat shock protein (hsp90 family)


heat shock protein HtpG


probable acetyltransferase


topoisomerase IV subunit B


1-deoxyxylulose-5-phosphate synthase


hypothetical protein


secretion protein SecD


heat shock protein HscA


probable binding protein component of ABC transporter


glucosamine-fructose-6-phosphate aminotransferase


transport protein MsbA


GTP-binding protein LepA


probable acyl-CoA dehydrogenase


succinate dehydrogenase (A subunit)


arginyl-tRNA synthetase


probable sodium/proton antiporter


probable acetyltransferase


penicillin-binding protein 3


conserved hypothetical protein


probable oxidoreductase


acetolactate synthase large subunit


single-stranded-DNA-specific exonuclease RecJ


prolyl-tRNA synthetase


urease alpha subunit


type 4 fimbrial biogenesis protein PilB


30S ribosomal protein S1


glutaminyl-tRNA synthetase


glucose-6-phosphate isomerase


hypothetical protein


electron transfer flavoprotein-ubiquinone oxidoreductase


GroEL protein


CTP synthase


probable chemotaxis transducer


arylsulfatase


conserved hypothetical protein


GMP synthase


hypothetical protein


probable carbohydrate kinase


phosphoglycerate mutase


conserved hypothetical protein


chromosomal replication initiator protein DnaA


ATP synthase alpha chain


hypothetical protein


apolipoprotein N-acyltransferase


hypothetical protein


xylulose kinase


general secretion pathway protein E


sodium/proton antiporter NhaB


probable colicin-like toxin


methylmalonate-semialdehyde dehydrogenase


RNA polymerase sigma-54 factor


probable transporter


N utilization substance protein A


hypothetical protein


probable flavin-binding monooxygenase


conserved hypothetical protein


UDP-N-acetylmuramoylalanyl-D-glutamate-2, 6-diaminopimelate ligase


hypothetical protein


probable amidase


outer membrane protein OprM precursor


RND divalent metal cation efflux membrane fusion protein CzcB


precursor


Glu-tRNA(Gln) amidotransferase subunit A


pyruvate kinase II


probable Mg transporter MgtE


Glu-tRNA(Gln) amidotransferase subunit B


UDP-N-acetylmuramate--alanine ligase


lipoamide dehydrogenase-glc


probable transporter (membrane subunit)


conserved hypothetical protein


probable outer membrane protein


probable ferredoxin


glutamine synthetase


probable type II secretion system protein


nitrite extrusion protein 2


probable amidase


soluble pyridine nucleotide transhydrogenase


replicative DNA helicase


probable glyceraldehyde-3-phosphate dehydrogenase


cysteinyl-tRNA synthetase


exodeoxyribonuclease VII large subunit


UDP-N-acetylmuramoylalanyl-D-glutamyl-2, 6-diaminopimelate--D-


alanyl-D-alanyl ligase


ATP synthase beta chain


signal recognition particle protein Ffh


adenylosucinate lyase


signal recognition particle receptor FtsY


probable 2-isopropylmalate synthase


conserved hypothetical protein


hypothetical protein


hypothetical protein


probable dicarboxylate transporter


biotin carboxylase


trytophanyl-tRNA synthetase


UDP-N-acetylmuramoylalanine-D-glutamate ligase


NADH dehydrogenase I chain F


probable aldolase


hypothetical protein


two-component response regulator PilR


phosphoglucosamine mutase


aminopeptidase P


probable cytochrome P450


conserved hypothetical protein


secretion protein SecY


hypothetical protein


probable MFS transporter


hypothetical protein


probable MFS transporter


porin O precursor


B-band O-antigen polymerase


conserved hypothetical protein


probable UDP-glucose/GDP-mannose dehydrogenase WbpA


probable binding protein component of ABC maltose/mannitol transporter


C4-dicarboxylate transport protein


conserved hypothetical protein


hypothetical protein


conserved hypothetical protein


TolB protein


hypothetical protein


adenylosuccinate synthetase


peptidyl-prolyl cis-trnas isomerase SurA


enolase


hypothetical protein


glutamate-1-semialdehyde 2,1 aminomutase


seryl-tRNA synthetase


3-deoxy-D-manno-octulosonic-acid (KDO) transferase


hypothetical protein


3-oxoacyl-acyl carrier protein synthase II


glutamyl-tRNA reductase


UDP-N-acetylglucosamine 1-carboxyvinyltransferase


hypothetical protein


transcription termination factor Rho


cell division protein FtsA


hypothetical protein


conserved hypothetical protein


ribonucleoside reductase, small chain


probable glycosyl transferase WbpJ


hypothetical protein


aspartate kinase alpha and beta chain


O-antigen translocase


hypothetical protein


hypothetical protein


probable transporter (membrane subunit)


conserved hypothetical protein


probable MFS transporter


conserved hypothetical protein


probable hydrolase


hypothetical protein


GTP-binding protein Obg


probable FAD-dependent monooxygenase


hypothetical protein


phenazine biosynthesis protein PhzC


probable type II secretion system protein


probable MFS transporter


conserved hypothetical protein


nitrate transporter


probable cytochrome b


hypothetical protein


DNA/pantothenate metabolism flavoprotein


membrane protein OpdE


two-component sensor


probable acyl-CoA thiolase


8-amino-7-oxononanoate synthase


conserved hypothetical protein


cell division protein FtsW


hypothetical protein


probable FAD-dependent monooxygenase


conserved hypothetical protein


probable MFS transporter


probable acyl-CoA thiolase


hypothetical protein


1-deoxy-d-xylulose 5-phosphate reductoisomerase


methionine adenosyltransferase


cell division protein FtsZ


hypothetical protein


probable pyridoxal-phosphate dependent enzyme


acetyl-CoA acetyltransferase


probable molybdopterin biosynthesis protein MoeB


conserved hypothetical protein


hypothetical protein


alginate biosynthesis protein Alg44


hypothetical protein


probable hydrolase


succinyl-CoA synthetase beta chain


hypothetical protein


probable ATP-binding component of ABC transporter


probable acyl-CoA dehydrogenase


phosphoglycerate kinase


hypothetical protein


hypothetical protein


probable RND efflux membrane fusion protein precursor


probable peptidic bond hydrolase


probable multidrug resistance efflux pump


succinyl-diaminopimelate desuccinylase


conserved hypothetical protein


probable acyl-CoA dehydrogenase


general secretion pathway protein L


proable permease of ABC transporter


erythronate-4-phosphate dehydrogenase


conserved hypothetical protein


hypothetical protein


probable acyl-CoA thiolase


conserved hypothetical protein


lipid A-disaccharide synthase


LPS biosynthesis protein WbpG


hypothetical protein


tRNA methyltransferase


probable acyl-CoA dehydrogenase


conserved hypothetical protein


conserved hypothetical protein


still frameshift type 4 fimbrial biogenesis protein PilC


cytochrome c oxidase, subunit II


conserved hypothetical protein


riboflavin-specific deaminase/reductase


probable glycosyltransferase WbpH


glycine cleavage system protein T2


muconate cycloisomerase I


UDP-glucose:(heptosyl) LPS alpha 1,3-glucosyltransferase WaaG


hypothetical protein


glutamate 5-kinase


conserved hypothetical protein


hypothetical protein


conserved hypothetical protein


hypothetical protein


aspartate semialdehyde dehydrogenase


rod shape-determining protein


alcohol dehydrogenase (Zn-dependent)


conserved hypothetical protein


hypothetical protein


peptide chain release factor 2


hypothetical protein


conserved hypothetical protein


hypothetical protein


conserved hypothetical protein


3-phosphoserine aminotransferase


peptide chain release factor 1


phospho-N-acetylmuramoyl-pentapeptide-transferase


hypothetical protein


probable aminotransferase WbpE


phospho-2-dehydro-3-doxyheptonate aldolase


O6-methylguanine-DNA methyltransferase


probable transcriptional regulator


UDP-N-acetylglucosamine-N-acetylmuramyl(pentapeptide) pyrophos-


phoryl-undecaprenol N-acetlyglucosasmine tr


uroporphyrinogen decarboxylase


hypothetical protein


heptosyltransferase I


conserved hypothetical protein


fructose-1,6-bisphosphate aldolase


type 4 fimbrial biogenesis protein PilM


probable UDP-N-acetylglucosamine 2-epimerase WbpI


phosphoribosylaminoimidazole synthetase


UDP-3-O-[3-hydroxylauroyl] glucosamine N-acyltransferase


quinolinate synthetase A


probable secretion protein


probable alcohol dehydrogenase (Zn-dependent)


conserved hypothetical protein


dTDP-D-glucose 4,6-dehydratase


outer membrane protein OprF precursor


hypothetical protein


conserved hypothetical protein


translocation protein in type III secretion


O-antigen chain length regulator


TolA protein


transcriptional regulator MexT


conserved hypothetical protein


acetylpolyamine aminohydrolase


conserved hypothetical protein


RecA protein


heptosyltransferase II


hypothetical protein


conserved hypothetical protein


rod shape-determining protein MreB


hypothetical protein


DNA polymerase III, delta subunit


tetrahydrodipicolinate succinylase


probable binding protein component of ABC transporter


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


delta 2-isopentenylpyrophosphate transferase


octaprenyl-diphosphate synthase


hypothetical protein


hypothetical protein


probable enoyl-CoA hydratase/isomerase


thiamine monophosphate kinase


hypothetical protein


hypothetical protein


hypothetical protein


probable serine/threonine dehydratase, degradative


pseudouridine synthase


conserved hypothetical protein


hypothetical protein


ribosomal large subunit pseudouridine synthase C


probable transcriptional regulator


hypothetical protein


probable transmembrane sensor


hypothetical protein


probable transcriptional regulator


probable transcriptional regulator


glutathione synthetase


hypothetical protein


probable adhesion protein


acetyl-coenzyme A carboxylase carboxyl transferase (alpha subunit)


probable transcriptional regulator


probable NAD-dependent epimerase/dehydratase WbpK


probable oxidoreductase WpbB


probable transmembrane sensor


hypothetical protein


glycyl-tRNA synthetase alpha chain


probable lipase


LytB protein


conserved hypothetical protein


probable hydrolase


ribose-phosphate pyrophosphokinase


hypothetical protein


conserved hypothetical protein


porphobilinogen deaminase


probable transcriptional regulator


probable lauroyl acyltransferase


transcriptional regulator PtxR


probable transcriptional regulator


hypothetical protein


malonyl-CoA-[acyl-carrier-protein] transacylase


riboflavin kinase/FAD synthase


conserved hypothetical protein


conserved hypothetical protein


probable phosphatidate cytidylyltransferase


hypothetical protein


carbamate kinase


hypothetical protein


probable transcriptional regulator


catechol 1,2 dioxygenase


D-alanyl-D-alanine-endopeptidase


probable transcriptional regulator


hypothetical protein


probable epimerase


lipase LipC


probable transcriptional regulator


electron transfer flavoprotein alpha-subunit


FdhE protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


probable ATP-binding component of ABC transporter


probable cytochrome c


probable transcriptional regulator


hypothetical protein


probable transcriptional regulator


probable permease of ABC transporter


hypothetical protein


probable transcriptional regulator


probable transcriptional regulator


probable transcriptional regulator


GTP-binding protein Era


probable transcriptional regulator


pyrroloquinoline quinone biosynthesis protein B


probable cytochrome c oxidase assembly factor


hypothetical protein


hypothetical protein


probable short chain dehydrogenase


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


UDP-3-O-acyl-N-acetylglucosamine deacetylase


probable transcriptional regulator


probable transcriptional regulator


conserved hypothetical protein


probable binding protein component of ABC transporter


dTDP-4-dehydrorhamnose reductase


conserved hypothetical protein


probable transcriptional regulator


hypothetical protein


hypothetical protein


probable transcriptional regulator


probable transferase


probable two-component response regulator


probable transcriptional regulator


hypothetical protein


cysteine synthase B


probable glycosyl transferase


TonB protein


O-sialoglycoprotein endopeptidase


ferrochelatase


conserved hypothetical protein


probable aminotransferase


probable transmembrane sensor


UDP-N-acetylpyruvoylglucosamine reductase


hypothetical protein


acetoin catabolism protein AcoB


conserved hypothetical protein


probable oxidoreductase


hypothetical protein


glycosyltransferase WbpL


hypothetical protein


probable transposase


flagellar motor switch protein FliG


hypothetical protein


probable transposase


probable transposase


probable transposase


probable transposase


phenylalanyl-tRNA synthetase, alpha-subunit


probable permease of ABC transporter


hypothetical protein


hypothetical protein


fructose-1,6-bisphosphatase


conserved hypothetical protein


probable ATP-binding component of ABC transporter


conserved hypothetical protein


hypothetical protein


probable O-methyltransferase


aspartate carbamoyltransferase


glyceraldehyde 3-phosphate dehydrogenase


conserved hypothetical protein


DNA-directed RNA polymerase alpha chain


probable pyruvate dehydrogenase E1 component, beta chain


tetraacyldisaccharide 4*-kinase


rod shape-determining protein MreC


D-lactate dehydrogenase (fermentative)


sulfate transport protein CysA


probable nucleoside hydrolase


pyridoxal phosphate biosynthetic protein PdxA


probable transmembrane sensor


DNA polymerase III, delta prime subunit


L-asparaginase I


hypothetical protein


probable bacteriophage integrase


lipoate synthase


hypothetical protein


conserved hypothetical protein


hypothetical protein


probable transcriptional regulator


hypothetical protein


probable transcriptional regulator


catechol 1,2-dioxygenase


D-alanyl-D-alanine-endopeptidase


probable transcriptional regulator


hypothetical protein


probable epimerase


lipase LipC


probable transcriptional regulator


electron transfer flavoprotein alpha-subunit


FdhE protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


probable ATP-binding component of ABC transporter


probable cytochrome c


probable transcriptional regulator


hypothetical protein


probable transcriptional regulator


probable permease of ABC transporter


hypothetical protein


probable transcriptional regulator


probable transcriptional regulator


probable transcriptional regulator


GTP-binding protein Era


probable transcriptional regulator


pyrroloquinoline quinone biosynthesis protein B


probable cytochrome c oxidase assembly factor


hypothetical protein


hypothetical protein


probable short chain dehydrogenase


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


UDP-3-O-acyl-N-acetylglucosamine deacetylase


probable transcriptional regulator


probable transcriptional regulator


conserved hypothetical protein


probable binding protein component of ABC transporter


dTDP-4-dehydrorhamnose reductase


conserved hypothetical protein


probable transcriptional regulator


hypothetical protein


hypothetical protein


probable transcriptional regulator


probable transferase


probable two-component response regulator


probable transcriptional regulator


hypothetical protein


cysteine synthase B


probable glycosyl transferase


hypothetical protein


probable transcriptional regulator


probable transcriptional regulator


probable transcriptional regulator


probable transcriptional regulator


probable transcriptional regulator


cytochrome o ubiquinol oxidase protein CyoE


probable-3-hydroxyisobutyrate dehydrogenase


probable transcriptional regulator


4-hydroxybenzoate-octaprenyl transferase


probable chemotaxis protein


conserved hypothetical protein


probable 2-OH-lauroyltransferase


probable transcriptional regulator


succinyl-CoA-synthetase alpha chain


conserved hypothetical protein


geranyltranstransferase


hypothetical protein


ribosomal protein L11 methyltransferase


glucose-1-phosphate thymidylyltransferase


conserved hypothetical protein


hypothetical protein


dihydrodipicolinate synthase


heat shock protein HtpX


methyltransferase PilK


probable transcriptional regulator


conserved hypothetical protein


hypothetical protein


chromosome partitioning protein SpoOJ


hypothetical protein


aetyl-CoA carboxylase beta subunit


elongation factor Ts


cell division protein ZipA


ATP synthase A chain


outer membrane protein PopN


lipase modulator protein


hypothetical protein


probable transcriptional regulator


conserved hypothetical protein


hypothetical protein


cell division protein FtsQ


malonate decarboxylase beta subunit


ATP synthase gamma chain


probable hydrolase


hypothetical protein


probable short-chain dehydrogenase


spermidine synthase


probable ATP-binding component of ABC transporter


hypothetical protein


hypothetical protein


probable ATP-binding component of ABC transporter


hypothetical protein


probable transcriptional regulator


5, 10-methylene-tetrahydrofolate dehydrogenase/cyclohydrase


sigma factor RpoH


signal peptidase I


hypothetical protein


formyltrahydrofolate deformylase


dihydropteroate synthase


conserved hypothetical protein


probable potassium channel


isopentenyl monophosphate kinase


hypothetical protein


hypothetical protein


nicotinate-nucleotide pyrophosphorylase


conserved hypothetical protein


hypothetical protein


2-dehydro-3-deoxyphosphooctonate aldolase


probable transmembrane sensor


urease accessory protein


flagellar synthesis regulator FleN


probable ATP-binding component of ABC transporter


probable phenazine biosynthesis protein


ATP-binding component of ABC phosphonate transporter


probable ATP-binding component of ABC transporter


probable permease of ABC transporter


probable short-chain dehydrogenase


diaminopimelate epimerase


probable two-component response regulator


conserved hypothetical protein


NH3-dependent NAD snthetase


NosY protein


probable biotin synthesis protein BioC


probable transcriptional regulator


type 4 fimbrial biogenesis protein PilW


probable chemotaxis protein methyltransferase


conserved hypothetical protein


50S ribosomal protein L2


hypothetical protein


probable oxidoreductase


probable permease of ABC taurine transporter


conserved hypothetical protein


hypothetical protein


hypothetical protein


phosphatidate cytidylyltransferase


phosphatidylserine synthase


hypothetical protein


thiosulfate sulfurtransferase


hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


probable transcriptional regulator


probable permease of ABC transporter


conserved hypothetical protein


probable transcriptional regulator


hypothetical protein


dihydrodipicolinate reductase


hypothetical protein


lipopolysaccharide core biosynthesis protein WaaP


tryptophan synthase alpha chain


probable ATP-binding component of ABC transporter


hypothetical protein


probable permease of ABC-2 transporter


probable transcriptional regulator


conserved hypothetical protein


prolipoprotein diacylglyceryl transferase


3-methyl-2-oxobutanoate hydroxymethyltransferase


glutamate racemase


conserved hypothetical protein


probable permease of ABC transporter


probable permease of ABC transporter


probable enoyl-CoA hydratase/isomerase


probable transcriptional regulator


conserved hypothetical protein


thymidylate synthase


hypothetical protein


hypothetical protein


probable enoyl-CoA hydratase/isomerase


translocation protein in type III secretion


hypothetical protein


probable pili assembly chaperone


probable transcriptional regulator


probable plasmid partitioning protein


probable permease of ABC transporter


conserved hypothetical protein


methionine aminopeptidase


conserved hypothetical protein


hypothetical protein


hypothetical protein


probable transcriptional regulator


probable permease of ABC-2 transporter


probable NAD(P)H dehydrogenase


conserved hypothetical protein


hypothetical protein


UDP-N-acetylglucosamine acyltransferase


ferredoxin—NADP + reductase


probable permease of ABC transporter


conserved hypothetical protein


probable enoyl-CoA hydratase/isomerase


polyamine transport protein PotC


ubiquinone biosynthesis methyltransferase UbiE


hypothetical protein


trnscriptional regulator PrtR


conserved hypothetical protein


probable transcriptional regulator


conserved hypothetical protein


probable exopolysaccharide transporter


probable ATP-binding component of ABC transporter


hypothetical protein


probable short-chain dehydrogenase


conserved hypothetical protein


3-deoxy-manno-octulosonate cytidylyltransferase


probable transporter


conserved hypothetical protein


probable transcriptional regulator


probable thioesterase


hypothetical protein


hypothetical protein


hypothetical protein


cis-1,2-dihydroxycyclohexa-3,4-diene carboxylate dehydrogenase


probable enoyl-CoA hydratase/isomerase


molybdopterin biosynthesis MoeB protein


probable short-chain dehydrogenase


conserved hypothetical protein


heme exporter protein CcmC


hypothetical protein


tRNA (guanine-N1)-methyltransferase


type 4 fimbrial biogenesis protein PilF


imidazoleglycerol-phosphate synthase, cyclase subunit


conserved hypothetical protein


triosephosphate isomerase


uroporphyrinoen-III synthetase


undecaprenyl pyrophosphate synthetase


hypothetical protein


probable cobalamin biosynthetic protein


hypothetical protein


hypothetical protein


hypothetical protein


probable short-chain dehydrogenase


hypothetical protein


electron transfer flavoprotein beta-subunit


conserved hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


3-oxoacyl-[acyl-carrier-protein] reductase


hypothetical protein


hypothetical protein


probable pili assembly chaperone


DNA polymerase III, epsilon chain


30S ribosomal protein S2


hypothetical protein


hypothetical protein


probable nucleoside phosphorylase


uridylate kinase


hypothetical protein


probable permease of ABC transporter


hypothetical protein


hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


transcriptional regulator RhlR


probable phosphoribosyl transferase


probable ATP-binding component of ABC transporter


conserved hypothetical protein


conserved hypothetical protein


hypothetical protein


probable biotin biosynthesis protein bioH


probable permease of ABC transporter


hypothetical protein


conserved hypothetical protein


ribonuclease PH


probable glutamine amidotransferase


conserved hypothetical protein


probable transcriptional regulator


conserved hypothetical protein


probable transcriptional regulator


DNA-specific endonuclease I


probable transcriptional regulator


hypothetical protein


hypothetical protein


probable pili assembly chaperone


probable two-component response regulator


phosphoribosylaminoimidazole-succinocarboxamide synthase


succinate dehydrogenase (B subunit)


hypothetical protein


conserved hypothetical protein


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


probable ATP-binding component of ABC transporter


heme exporter protein CcmA


hypothetical protein


hypothetical protein


probable transcriptional regulator


3-demethylubiquinone-9 3-methyltransterase


probable hydrolase


orotidine 5′-phosphate decarboxylase


hypothetical protein


hypothetical protein


50S ribosomal protein L1


conserved hypothetical protein


probable permease of ABC transporter


hypothetical protein


probable acetyltransferase


hypothetical protein


TolQ protein


hypothetical protein


conserved hypothetical protein


hypothetical protein


probable pseudouridylate synthase


cytidylate kinase


hypothetical protein


two-component response regulator


30S ribosomal protein S3


hypothetical protein


probable transcriptional regulator


dethiobiotin synthase


molybdenum transport protein ModB


transcriptional regulator Dnr


hypothetical protein


probable ATP-binding component of ABC transporter


leucyl/phenylalanyl-tRNA-protein transferase


conserved hypothetical protein


NADH dehydrogenase I chain B


probable two-component response regulator


hypothetical protein


probable transcriptional regulator


Na+-translocating NADH:uniquinone oxidoreductase subunit Nqr4


ribonuclease T


hypothetical protein


conserved hypothetical protein


DNA repair protein RadC


ribulose-phosphate 3-epimerase


hypothetical protein


hypothetical protein


heme exporter protein CcmB


hypothetical protein


urease accessory protein UreF


ribose 5-phosphate isomerase


phosphoribosylaminoimidazole synthetase


probable transcriptional regulator


probable transcriptional regulator


probable transcriptional regulator


hypothetical protein


conserved hypothetical protein


probable acetyltransferase


probable transcriptional regulator


probable two-component response regulator


conserved hypothetical protein


2-keto-3-deoxy-6-phosphogluconate aldolase


probable permease of ABC transporter


hypothetical protein


hypothetical protein


probable transcriptional regulator


hypothetical protein


hypothetical protein


riboflavin synthase alpha chain


conserved hypothetical protein


thiopurine methyltransferase


probable permease of ABC transporter


alginate o-acetyltransferase AlgF


conserved hypothetical protein


conserved hypothetical protein


probable transcriptional regulator


pyridoxine 5′-phosphate oxidase


hypothetical protein


hypothetical protein


probable carboxylesterase


pyoverdine biosynthesis protein PvcD


probable transcriptional regulator


probable carbonic anhydrase


conserved hypothetical protein


probable pyridoxamine 5′-phosphate oxidase


probable pyridoxamine 5′-phosphate oxidase


hypothetical protein


probable glutathione S-transferase


hypothetical protein


transcriptional regulator Vfr


hypothetical protein


orotate phoshoribosyltransferase


glutamine amidotransferase


hypothetical protein


hypothetical protein


maleylacetoacetate isomerase


probable radical activating enzyme


hypothetical protein


uracil phosphoribosyltransferase


hypothetical protein


endonuclease III


probable transcrptional regulator


probable antioxidant protein


hypothetical protein


conserved hypothetical protein


hypothetical protein


probable tolQ-type transport protein


pseudouridine synthase RluA


conserved hypothetical protein


50S ribosomal protein L3


conserved hypothetical protein


hypothetical protein


hypothetical protein


probable two-component response regulator


thymidylate kinase


conserved hypothetical protein


conserved hypothetical protein


probable aromatic acid decarboxdase


hypothetical protein


probable nuclease


periplasmic chaperone LolA


hypothetical protein


probable oxidoreductase


hypothetical protein


hypothetical protein


cell division protein FtsJ


hypothetical protein


hypothetical protein


hypothetical protein


30S ribosomal protein S4


homoserine kinase


hypothetical protein


probable lipoprotein localization protein LolB


stringent starvation protein A


hypothetical protein


GTP cyclohydrolase II


hypothetical protein


heme acquisition protein HasAp


probable transcriptional regulator


probable peptide chain release factor


probable ribosomal protein L25


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


guanylate kinase


glutamine amidotransferase


conserved hypothetical protein


hypothetical protein


protocatechuate 3,4-dioxygenase, alpha subunit


hypothetical protein


autoinducer synthesis protein LasI


probable Clp-family ATP-dependent protease


hypothetical protein


50S ribosomal protein L4


conserved hypothetical protein


probable nitroreductase


hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


probable molybdopterin-guanine dinucleotide biosynthesis protein MobA


hypothetical protein


cytochrome c-type protein NapC


conserved hypothetical protein


hypothetical protein


hypothetical protein


probable phosphoheptose isomerase


ribosome recycling factor


conserved hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


probable transcriptional regulator


conserved hypothetical protein


hypothetical protein


translation initiation factor IF-3


potassium-transporting ATPase, C chain


probable transcriptional regulator


conserved hypothetical protein


conserved hypothetical protein


adenine phosphoribosyltransferase


conserved hypothetical protein


dTDP-4-dehydrorhamnose 3,5-epimerase


hypothetical protein


probable sigma-70 factor, ECF subfamily


GTP cyclohydrolase I precursor


hypothetical protein


cytochrome C biogenesis protein CcmG


conserved hypothetical protein


50S ribosomal protein L5


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


ATP synthase delta chain


NosL protein


conserved hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


50S ribosomal protein L6


conserved hypothetical protein


conserved hypothetical protein


transcription antitermination protein NusG


hypothetical protein


hypothetical protein


conserved hypothetical protein


lactoylglutathione lyase


outer membrane lipoprotein OmlA


hypothetical protein


inoranic pyrophosphatase


probable sigma-70 factor, ECF subfamily


conserved hypothetical protein


conserved hypothetical protein


hypothetical protein


16S rRNA processing protein


hypothetical protein


hypothetical protein


heme d1 biosynthesis protein NirL


hypothetical protein


hypothetical protein


general secretion pathway protein M


hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


heat shock protein HscB


hypothetical protein


hypothetical protein


general secretion pathway protein H


conserved hypothetical protein


shikimate kinase


hypothetical protein


conserved hypothetical protein


phosphatidylglycerophosphatase A


beta-hydroxydecanoyl-ACP dehydrase


conserved hypothetical protein


transcriptional regulator PyrR


conserved hypothetical protein


spermidine acetyltransferase


prolipoprotein signal peptidase


hypothetical protein


conserved hypothetical protein


probable transcriptional regulator


conserved hypothetical protein


probable sigma-70 factor, ECF subfamily


conserved hypothetical protein


hypothetical protein


hypothetical protein


probable outer membrane protein precursor


probable outer membrane protein


hypothetical protein


transcription elongation factor GreB


dihydrofolate reductase


hypothetical protein


hypothetical protein


50S ribosomal protein L10


30S ribosomal protein S5


hypothetical protein


hypothetical protein


hypothetical protein


NADH dehydrogenase I chain J


hypothetical protein


hypothetical protein


hypothetical protein


single-stranded DNA-binding protein


hypothetical protein


secretion protein SecB


conserved hypothetical protein


cytochrome c-type protein NapB precursor


ferredoxin protein NapF


probable methyltransferase


probable phenazine biosynthesis protein


probable phenazine biosynthesis protein


probable phenazine biosynthesis protein


hypothetical protein


hypothetical protein


probable phenazine biosynthesis protein


conserved hypothetical protein


toluate 1,2-dioxygenase beta subunit


2-amino-4-hydroxy-6-hydroxymethyldihydropterdine pyrophosphoknase


hypothetical protein


peptidyl-prolyl cis-trans isomerase SlyD


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


molybdopterin biosynthetic protein C


conserved hypothetical protein


hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


NusB protein


phosphopantetheine adenylyltransferase


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


hypothetical protein


probable purine-binding chemotaxis protein


hypothetical protein


hypothetical protein


hypothetical protein


6,7-dimethyl-8-ribityllumazine synthase


hypothetical protein


conserved hypothetical protein


translocation protein in type III secretion


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


bacterioferritin comigratory protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


ATP synthase B chain


30S ribosomal protein S7


cyanate lyase


biotin carboxyl carrier protein (BCCP)


probable dna-binding stress protein


hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


cytochrome C-type biogenesis protein CcmH


hypothetical protein


hypothetical protein


hypothetical protein


probable thioredoxin


conserved hypothetical protein


hypothetical protein


nitrogen regulatory IIA protein


hypothetical protein


conserved hypothetical protein


phosphotyrosine protein phosphatase


probable HIT family protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


hypothetical protein


probable deaminase


conserved hypothetical protein


conserved hypothetical protein


osmotically inducible protein OsmC


deoxyuridine 5′-triphosphate nucleotidohydrolase


conserved hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


molybdopterin converting factor, large subunit


conserved hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


probable type II secretion system protein


type 4 fimbrial precursor PilA


probable transcriptional regulator


hypothetical protein


hypothetical protein


3-dehydroquinate dehydratase


ribonuclease H


hypothetical protein


hypothetical protein


probable peptide deformylase


probable transcriptional regulator


flagellar protein FliJ


TolR protein


conserved hypothetical protein


(3R)-hydroxymyristoyl-[acyl carrier protein] dehydratase


hypothetical protein


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


probable transcriptional regulator


conserved hypothetical protein


hypothetical protein


exoenzyme S synthesis protein C precursor


probable transcriptional regulator


hypothetical protein


hypothetical protein


50S ribosomal protein L15


hypothetical protein


conservedl hypothetical protein


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


hypothetical protein


probable type II secretion system protein


helix destabilizing protein of bacteriophage Pf1


hypothetical protein


nucleoside diphosphate kinase


50S ribosomal protein L11


hypothetical protein


hypothetical protein


50S ribosomal protein L13


hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


probable transcriptional regulator


hypothetical protein


probable type II secretion system protein


hypothetical protein


ATP synthase epsilon chain


hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


hypothetical protein


30S ribosomal protein S6


hypothetical protein


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


hypothetical protein


50S ribosomal protein L16


hypothetical protein


probable type II secretion system protein


hypothetical protein


cytochrome c5


hypothetical protein


hypothetical protein


hypothetical protein


ribonuclease P protein component


stringent starvation protein B


probable fosfomycin resistance protein


hypothetical protein


hypothetical protein


hypothetical protein


ferric uptake regulation protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


probable transcriptional regulator


probable NADH-ubiquinone/plastoquinone oxidoreductase


hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


probable transcriptional regulator


hypothetical protein


hypothetical protein


alkaline proteinase inhibitor AprI


lactoylglutathione lyase


hypothetical protein


hypothetical protein


hypothetical protein


probable heat shock protein


hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


30S ribosomal protein S8


hypothetical protein


5-carboxymethyl-2-hydroxymuconate isomerase


30S ribosomal pretein S9


hypothetical protein


hypothetical protein


probable cytochrome c(monoheme type)


30S ribosomal protein S11


50S ribosomal protein L17


secretion protein SecG


hypothetical protein


hypothetical protein


hypothetical protein


probable iron-binding protein lscU


succinate dehydrogenase (C subunit)


hypothetical protein


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


glycine cleavage system protein H2


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


aspartate 1-decarboxylase precursor


hypothetical protein


hypothetical protein


conserved hypothetical protein


probable ring-cleaving dioxygenase


hypothetical protein


ATP synthase protein I


conserved hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


probable type II secretion system protein


hypothetical protein


two-component response regulator CheY


hypothetical protein


hypothetical protein


transcriptional regulator MvaT, P16 subunit


d-erythro-7,8-dihydroneopterin triphosphate epimerase


30S ribosomal protein S12


conserved hypothetical protein


hypothetical protein


hypothetical protein


probable drug efflux transporter


50S ribosomal protein L14


hypothetical protein


hypothetical protein


50S ribosomal protein L7/L12


secretion protein SecE


succinate dehydrogeriase (D subunit)


hypothetical protein


hypothetical protein


conserved hypothetical protein in type III secretion


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


50S ribosomal protein L20


probable 6-pyruvoyl tetrahydrobiopterin synthase


hypothetical protein


30S ribosomal protein S13


type 4 fimbrial biogenesis protein PilZ


pterin-4-alpha-carbinolamine dehydratase


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


dihydroneopterin aldolase


conserved hypothetical protein


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


50S ribosomal protein L18


conserved hypothetical protein


50S ribosomal protein L19


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


type III export protein PscG


hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


probable ferredoxin


nitrogen regulatory protein P-II 2


ferredoxin [2Fe-2S]


conserved hypothetical protein


conserved hypothetical protein


type III export protein PscI


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


phosphoribosyl-ATP pyrophosphohydrolase


conserved hypothetical protein


50S ribosomal protein L22


SMR multidrug efflux transporter


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


hypothetical protein


conserved hypothetical protein


conserved hypothetical protein


hypothetical protein


conserved hypothetical protein in type III secretion


conserved hypothetical protein


hypothetical protein


hypothetical protein


assimilatory nitrite reductase small subunit


hypothetical protein


conserved hypothetical protein


probable thioredoxin


thioredoxin


probable bacteriophage protein


conserved hypothetical protein


hypothetical protein


probable transporter


















TABLE 3





Mutant Name
Insertion Point
host strain

















001A01
3254036
PAK


001A03
4214526
PAK


001A04
800208
PAK


001A05
3627210
PAK


001A06
4931913
PAK


001A07
1034469
PAK


001A08
6144940
PAK


001A09
4102307
PAK


001A11
1515737
PAK


001A12
1244688
PAK


001B02
5924618
PAK


001B03
3267350
PAK


001B04
3302119
PAK


001B05
3108121
PAK


001B06
3987545
PAK


001B07
5585518
PAK


001B09
4682141
PAK


001B10
5041902
PAK


001B11
3187871
PAK


001C01
5924618
PAK


001C02
2871514
PAK


001C03
474619
PAK


001C04
5156931
PAK


001C05
6155744
PAK


001C06
5741543
PAK


001C08
594556
PAK


001C09
2370763
PAK


001C10
4186878
PAK


001C11
2016482
PAK


001C12
5610441
PAK


001D01
6193619
PAK


001D03
6078034
PAK


001D04
6139878
PAK


001D05
522531
PAK


001D06
3567982
PAK


001D08
3998726
PAK


001D09
2140251
PAK


001D10
1301169
PAK


001D11
3423519
PAK


001D12
3472670
PAK


001E02
800936
PAK


001E03
4246525
PAK


001E04
477959
PAK


001E05
477959
PAK


001E06
5939777
PAK


001E07
5471284
PAK


001E08
5582311
PAK


001E09
442285
PAK


001E10
4514879
PAK


001E11
4514879
PAK


001E12
5064081
PAK


001F01
903376
PAK


001F02
1889581
PAK


001F03
1230813
PAK


001F04
5755640
PAK


001F05
5355403
PAK


001F06
4493238
PAK


001F07
850016
PAK


001F08
5286479
PAK


001F09
3035834
PAK


001F10
270414
PAK


001F11
4300290
PAK


001F12
34717403
PAK


001G01
5431778
PAK


001G06
5064081
PAK


001G07
353196
PAK


001G08
4881356
PAK


001G09
4684466
PAK


001G10
1340542
PAK


001G11
2659761
PAK


001G12
4553600
PAK


001G01
5431778
PAK


001G02
627197
PAK


001G03
3005616
PAK


001G05
2300131
PAK


001G06
5064081
PAK


001G07
3531951
PAK


001G08
4881356
PAK


001G09
4684465
PAK


001H01
4600925
PAK


001H02
4465691
PAK


001H03
435295
PAK


001H04
5583961
PAK


001H06
5823734
PAK


001H08
3880466
PAK


001H09
271720
PAK


001H10
433381
PAK


001H11
395319
PAK


002A01
3652524
PAK


002A02
3987593
PAK


002A03
530429
PAK


002A04
6232877
PAK


002A05
1543845
PAK


002A06
619210
PAK


002A07
4795351
PAK


002A09
1152202
PAK


002A10
1205010
PAK


002A11
449470
PAK


002B01
5643797
PAK


002B02
3423910
PAK


002B03
3616916
PAK


002B04
1511758
PAK


002B05
3809953
PAK


002B06
127793
PAK


002B07
1277942
PAK


002B08
5436760
PAK


002B09
1030808
PAK


002B10
1030806
PAK


002B11
3355560
PAK


002B12
3935624
PAK


003A01
2016406
PAK


003A02
4987284
PAK


003A03
1713832
PAK


003A04
1859681
PAK


003A05
433381
PAK


003A06
6241260
PAK


003A08
1026213
PAK


003A09
4822426
PAK


003A10
513656
PAK


003A11
5050248
PAK


003B04
3377875
PAK


003B06
1969305
PAK


003B07
433381
PAK


003B08
1034469
PAK


003B09
5907415
PAK


003B10
4192241
PAK


003B11
4192241
PAK


003C01
5713913
PAK


003C02
2609592
PAK


003C03
2095164
PAK


003C04
5369447
PAK


003C05
799610
PAK


003C07
2410828
PAK


003C08
1576887
PAK


003C09
3998623
PAK


003C10
3771149
PAK


003C11
1408282
PAK


003C12
814349
PAK


003D01
433382
PAK


003D02
259586
PAK


003D03
1700770
PAK


003D04
433381
PAK


003D05
4893664
PAK


003D07
810409
PAK


003D08
433381
PAK


003D09
5970386
PAK


003D12
2049456
PAK


003E01
1819428
PAK


003E03
2555440
PAK


003E06
5415888
PAK


003E07
5929820
PAK


003E08
5414529
PAK


003E09
835119
PAK


003E10
4855368
PAK


003E12
5159655
PAK


003F01
683274
PAK


003F02
1428758
PAK


003F04
4638260
PAK


003F05
2695523
PAK


003F07
3607969
PAK


003F08
1082510
PAK


003F09
1031737
PAK


003F10
433381
PAK


003F11
3422289
PAK


003F12
2922974
PAK


003G01
4707158
PAK


003G02
5428282
PAK


003G04
5649040
PAK


003G05
433381
PAK


003G06
2581798
PAK


003G07
648767
PAK


003G10
5758975
PAK


003G11
6015681
PAK


003G12
6139731
PAK


003H01
3445197
PAK


003H02
1525921
PAK


003H03
5315736
PAK


003H04
1291849
PAK


003H05
30684
PAK


003H06
3266054
PAK


003H07
2049456
PAK


003H08
433381
PAK


003H09
879532
PAK


004A01
1566541
PAK


004A03
1503899
PAK


004A04
45765
PAK


004A05
5735233
PAK


004A06
5075716
PAK


004A07
2157575
PAK


004A08
3471740
PAK


004A09
2271949
PAK


004A10
2796245
PAK


004A11
4454450
PAK


004B01
5951238
PAK


004B02
1351731
PAK


004B04
433381
PAK


004B05
2848857
PAK


004B06
732379
PAK


004B07
4316856
PAK


004B08
4550848
PAK


004B09
5223972
PAK


004B12
454432
PAK


004C01
3293171
PAK


004C03
1835520
PAK


004C04
2188343
PAK


004C05
3047374
PAK


004C06
5315858
PAK


004C09
1460144
PAK


004C10
2049699
PAK


004C11
5988345
PAK


004C12
1104579
PAK


004D01
751552
PAK


004D02
3944498
PAK


004D03
1883754
PAK


004D04
910624
PAK


004D05
5437535
PAK


004D06
5097189
PAK


004D07
5397511
PAK


004D08
4193733
PAK


004D09
3400490
PAK


004D10
5308284
PAK


004D11
5859357
PAK


004D12
4364415
PAK


004E01
3312704
PAK


004E04
1566516
PAK


004E05
5799481
PAK


004E06
1897781
PAK


004E08
1166054
PAK


004E09
5865140
PAK


004E10
2471733
PAK


004E11
5956163
PAK


004E12
1653588
PAK


004F01
5865145
PAK


004F06
1122958
PAK


004F07
1884758
PAK


004F08
156187
PAK


004F09
3723875
PAK


004F11
1034468
PAK


004F12
3047374
PAK


004G02
6100910
PAK


004G03
3885608
PAK


004G06
5004165
PAK


004G07
629956
PAK


004G09
2231219
PAK


004G11
5772930
PAK


004G12
392997
PAK


004H02
1595508
PAK


004H03
1595508
PAK


004H04
3635403
PAK


004H05
5988173
PAK


004H06
1821975
PAK


004H08
5150834
PAK


004H09
422703
PAK


004H10
5511104
PAK


004H11
395319
PAK


005A01
6121145
PAK


005A02
4637976
PAK


005A03
5251656
PAK


005A04
1358579
PAK


005A05
2826665
PAK


005A06
351028
PAK


005A08
2009564
PAK


005A09
1779817
PAK


005A11
2636229
PAK


005A12
3726006
PAK


005B03
4797603
PAK


005B05
1423578
PAK


005B06
1086897
PAK


005B07
3463110
PAK


005B08
1490094
PAK


005B09
1583954
PAK


005B10
681527
PAK


005B11
2537467
PAK


005B12
6223150
PAK


005C02
1445969
PAK


005C03
6112259
PAK


005C04
4104568
PAK


005C07
260868
PAK


005C08
1659915
PAK


005C09
6978331
PAK


005C10
3642669
PAK


005C11
543492
PAK


005C12
543492
PAK


005D01
1739361
PAK


005D02
4375879
PAK


005D03
2854969
PAK


005D04
3183786
PAK


005D05
3715903
PAK


005D06
45493251
PAK


005D08
806743
PAK


005D10
5054137
PAK


005D11
5218315
PAK


005D12
4981489
PAK


005E03
7475951
PAK


005E04
19912441
PAK


005E05
7475951
PAK


005E06
5945978
PAK


005E07
3075241
PAK


005E09
1868247
PAK


005E11
3306428
PAK


005E12
947510
PAK


005F01
3225856
PAK


005F03
1309650
PAK


005F04
3709087
PAK


005F05
5077881
PAK


005F08
1680865
PAK


005F10
2185333
PAK


005F11
4299947
PAK


005F12
1130487
PAK


005G02
5018107
PAK


005G03
4422899
PAK


005G06
4517577
PAK


005G07
5059743
PAK


005G08
1843340
PAK


005G09
6107697
PAK


005G10
4364428
PAK


005G11
4026064
PAK


005G12
1099396
PAK


005H03
6214274
PAK


005H04
2144520
PAK


005H05
1807286
PAK


005H06
1807286
PAK


005H08
3699645
PAK


005H10
1515737
PAK


005H11
395319
PAK


006A01
6231371
PAK


006A02
3402303
PAK


006A04
2079699
PAK


006A05
2008375
PAK


006A06
433381
PAK


006A08
3592139
PAK


006A09
3453875
PAK


006A10
794950
PAK


006A11
5819801
PAK


006A12
3468427
PAK


006B01
1966899
PAK


006B02
3160110
PAK


006B03
2955666
PAK


006B04
3511738
PAK


006B05
4241233
PAK


006B06
2471515
PAK


006B07
2048265
PAK


006B08
2469575
PAK


006B09
696492
PAK


006B10
846315
PAK


006B11
166648
PAK


006B12
4741112
PAK


006C01
433381
PAK


006C02
4064994
PAK


006C03
1280374
PAK


006C04
3596440
PAK


006C05
1442814
PAK


006C07
577497
PAK


006C09
1784068
PAK


006C10
2240534
PAK


006C12
4047002
PAK


006D01
4070007
PAK


006D02
6085314
PAK


006D03
1150463
PAK


006D05
3610871
PAK


006D06
5310625
PAK


006D07
517361
PAK


006D08
2892863
PAK


006D09
3327334
PAK


006D10
2229992
PAK


006D11
1878712
PAK


006D12
3916203
PAK


006E01
147621
PAK


006E02
147622
PAK


006E03
688108
PAK


006E04
688115
PAK


006E06
5023473
PAK


006E11
4844174
PAK


006F03
6230087
PAK


006F06
6257292
PAK


006F07
3086149
PAK


006F10
3020409
PAK


006F11
5211588
PAK


006F12
5211588
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061B06
670178
PAK pili-


061B07
750339
PAK pili-


061B08
6237574
PAK pili-


061B09
434887
PAK pili-


061B10
2594806
PAK pili-


061B11
2602819
PAK pili-


061C02
3669701
PAK pili-


061C03
5501059
PAK pili-


061C04
6240453
PAK pili-


061C05
339409
PAK pili-


061C06
970713
PAK pili-


061C07
5991897
PAK pili-


061C08
3845716
PAK pili-


061C09
1987268
PAK pili-


061C10
2216666
PAK pili-


061C11
1674612
PAK pili-


061C12
4185549
PAK pili-


061D02
3970481
PAK pili-


061D03
1561309
PAK pili-


061D04
4524167
PAK pili-


061D06
4401199
PAK pili-


061D07
4660568
PAK pili-


061D08
5835996
PAK pili-


061D09
3441962
PAK pili-


061D10
4322962
PAK pili-


061D11
5033212
PAK pili-


061D12
2708820
PAK pili-


061E01
6162007
PAK pili-


061E02
2398557
PAK pili-


061E04
472365
PAK pili-


061E05
1782511
PAK pili-


061E06
5930919
PAK pili-


061E07
1146276
PAK pili-


061E08
4521488
PAK pili-


061E09
4717236
PAK pili-


061E11
4380032
PAK pili-


061E12
4044343
PAK pili-


061F01
3301676
PAK pili-


061F02
5828638
PAK pili-


061F03
5634333
PAK pili-


061F04
5318976
PAK pili-


061F05
3420298
PAK pili-


061F06
6028099
PAK pili-


061F09
2874916
PAK pili-


061F10
1702230
PAK pili-


061F11
164740
PAK pili-


061F12
4169592
PAK pili-


061G05
2126206
PAK pili-


061G07
815297
PAK pili-


061G08
6260187
PAK pili-


061G09
1347823
PAK pili-


061G10
3775399
PAK pili-


061G11
4218405
PAK pili-


061G12
1166408
PAK pili-


061H01
5609073
PAK pili-


061H02
4186785
PAK pili-


061H03
3069909
PAK pili-


061H04
6121348
PAK pili-


061H05
2909905
PAK pili-


061H06
790965
PAK pili-


061H07
2061539
PAK pili-


061H08
2874916
PAK pili-


061H09
245693
PAK pili-


061H10
5207481
PAK pili-


061H11
395318
PAK pili-


062A01
522496
PAK pili-


062A02
2186046
PAK pili-


062A03
881650
PAK pili-


062A04
108711
PAK pili-


062A05
4573163
PAK pili-


062A06
4592778
PAK pili-


062A07
2767284
PAK pili-


062A08
245488
PAK pili-


062A09
245488
PAK pili-


062A11
4883451
PAK pili-


062A12
245488
PAK pili-


062B01
5814642
PAK pili-


062B02
972216
PAK pili-


062B03
2482611
PAK pili-


062B04
3763613
PAK pili-


062B07
6163753
PAK pili-


062B08
4880267
PAK pili-


062B09
3363603
PAK pili-


062B10
202392
PAK pili-


062B11
245488
PAK pili-


062C01
2796578
PAK pili-


062C02
1421710
PAK pili-


062C03
6193624
PAK pili-


062C04
4335461
PAK pili-


062C05
5582809
PAK pili-


062C06
1887384
PAK pili-


062C07
2674834
PAK pili-


062C08
3594859
PAK pili-


062C10
6126368
PAK pili-


062C11
6126368
PAK pili-


062C12
6126368
PAK pili-


062D01
3063043
PAK pili-


062D02
150387
PAK pili-


062D03
4879780
PAK pili-


062D06
5522349
PAK pili-


062D07
5567212
PAK pili-


062D09
6126368
PAK pili-


062D10
6126368
PAK pili-


062D11
6126368
PAK pili-


062D12
6126368
PAK pili-


062E05
245488
PAK pili-


062E06
4351023
PAK pili-


062E07
2219268
PAK pili-


062E08
6126368
PAK pili-


062E09
6126368
PAK pili-


062E10
61263631
PAK pili-


062E11
6126368
PAK pili-


062E12
6126368
PAK pili-


062F01
434886
PAK pili-


062F02
577228
PAK pili-


062F03
1460121
PAK pili-


062F06
6126368
PAK pili-


062F07
6126368
PAK pili-


062F08
6126363
PAK pili-


062F09
6126368
PAK pili-


062F10
6126368
PAK pili-


062F11
6126368
PAK pili-


062F12
6126370
PAK pili-


062G01
1283697
PAK pili-


062G04
6126368
PAK pili-


062G05
6126368
PAK pili-


062G06
6126368
PAK pili-


062G07
6126368
PAK pili-


062G08
6126368
PAK pili-


062G09
6126368
PAK pili-


062G10
6126368
PAK pili-


062G11
6126368
PAK pili-


062G12
6126368
PAK pili-


062H01
1838755
PAK pili-


062H02
3931380
PAK pili-


062H03
205757
PAK pili-


062H05
6126368
PAK pili-


062H06
6126368
PAK pili-


062H07
6126368
PAK pili-


062H08
6126368
PAK pili-


062H09
6126368
PAK pili-


062H10
6126368
PAK pili-


062H11
6126368
PAK pili-


063A01
1864595
PAK


063A02
4577583
PAK


063A03
4623271
PAK


063A05
6187365
PAK


063A07
4396482
PAK


063A08
980960
PAK


063A09
5389145
PAK


063A10
37148051
PAK


063A11
4859681
PAK


063A12
703497
PAK


063B01
58161
PAK


063B02
2480836
PAK


063B03
964761
PAK


063B04
4323451
PAK


063B05
3867238
PAK


063B07
5201475
PAK


063B08
5389781
PAK


063B11
404986
PAK


063C01
3837626
PAK


063C02
467401
PAK


063C05
617809
PAK


063C08
5817926
PAK


063C09
5976549
PAK


063C10
4691492
PAK


063C12
6135396
PAK


063D02
890907
PAK


063D03
820642
PAK


063D05
6188347
PAK


063D06
3418092
PAK


063D07
1099496
PAK


063D08
4185902
PAK


063D12
4828824
PAK


063E02
380103
PAK


063E05
5457853
PAK


063E06
1292848
PAK


063E07
5861274
PAK


063E09
5485515
PAK


063E10
662186
PAK


063E11
58104
PAK


063E12
3831435
PAK


063F01
3919920
PAK


063F02
4301739
PAK


063F04
4280034
PAK


063F05
1158788
PAK


063F07
6064109
PAK


063F08
3414689
PAK


063F10
5035262
PAK


063F11
3813526
PAK


063F12
6140999
PAK


063G02
1857879
PAK


063G03
080687
PAK


063G04
3640119
PAK


063G05
1265153
PAK


063G07
4508353
PAK


063G09
1317210
PAK


063G10
3050895
PAK


063G11
4019209
PAK


063H01
3634874
PAK


063H02
152357
PAK


063H03
3886848
PAK


063H04
5124231
PAK


063H06
6085999
PAK


063H07
2789478
PAK


063H10
5580029
PAK


064A01
910928
PAK


064A02
855436
PAK


064A03
5924276
PAK


064A04
3633746
PAK


064A05
4106446
PAK


064A06
5179182
PAK


064A07
1276940
PAK


064A09
619609
PAK


064A10
1149850
PAK


064A11
2559980
PAK


064A12
3390116
PAK


064B01
6127019
PAK


064B02
4236620
PAK


064B03
5340297
PAK


064B04
4363981
PAK


064B06
5605621
PAK


064B07
4571866
PAK


064B09
3257360
PAK


064B11
306854
PAK


064B12
2375623
PAK


064C01
4102306
PAK


064C02
3048716
PAK


064C04
4538704
PAK


064C05
1780529
PAK


064C06
178052
PAK


064C07
576267
PAK


064C09
4687072
PAK


064C10
5126155
PAK


064C11
3679268
PAK


064D01
5081539
PAK


064D02
6104666
PAK


064D03
2266420
PAK


064D04
1770947
PAK


064D05
5407726
PAK


064D06
3215213
PAK


064D07
1077640
PAK


064D09
2904482
PAK


064D10
4303847
PAK


064D12
1713618
PAK


064E01
179957
PAK


064E02
2905531
PAK


064E03
5293460
PAK


064E04
3453385
PAK


064E05
1045916
PAK


064E07
3153585
PAK


064E08
6234787
PAK


064E10
1025545
PAK


064F02
1832530
PAK


064F03
4617041
PAK


064F04
2503673
PAK


064F06
560354
PAK


064F07
2020127
PAK


064F08
2583822
PAK


064F09
2532110
PAK


064F10
3213745
PAK


064F12
953205
PAK


064G01
3274554
PAK


064G02
154806
PAK


064G05
751816
PAK


064G06
2839349
PAK


064G07
3315574
PAK


064G08
5129696
PAK


064G09
5815721
PAK


064G10
1292321
PAK


064G11
273012
PAK


064G12
5258655
PAK


064H02
864263
PAK


064H04
325492
PAK


064H05
4881106
PAK


064H06
5300816
PAK


064H07
2322929
PAK


064H08
6056031
PAK


064H09
338714
PAK


064H10
4239063
PAK


065A01
213053
PAK pili-


065A02
102027
PAK pili-


065A03
3561848
PAK pili-


065A04
2827456
PAK pili-


065A05
3691872
PAK pili-


065A06
3811269
PAK pili-


065A09
634047
PAK pili-


065A10
2365466
PAK pili-


065A11
2856356
PAK pili-


065A12
1465531
PAK pili-


065B01
5427483
PAK pili-


065B02
6109641
PAK pili-


065B03
895717
PAK pili-


065B04
4661329
PAK pili-


065B05
3373867
PAK pili-


065B06
4683526
PAK pili-


065B07
3755105
PAK pili-


065B09
931497
PAK pili-


065B10
3147506
PAK pili-


065B12
4156896
PAK pili-


065C01
2880194
PAK pili-


065C02
3153395
PAK pili-


065C03
740899
PAK pili-


065C04
2374394
PAK pili-


065C05
5476873
PAK pili-


065C07
583110
PAK pili-


065C08
2511899
PAK pili-


065C09
1578675
PAK pili-


065C10
4248094
PAK pili-


065C11
867526
PAK pili-


065C12
1133179
PAK pili-


065D03
5431177
PAK pili-


065D05
4194736
PAK pili-


065D06
40556
PAK pili-


065D07
2531813
PAK pili-


065D08
1493098
PAK pili-


065D10
330197
PAK pili-


065D11
220703
PAK pili-


065D12
6036810
PAK pili-


065E01
2913469
PAK pili-


065E02
4821487
PAK pili-


065E03
5815961
PAK pili-


065E04
1472344
PAK pili-


065E06
197187
PAK pili-


065E07
5493474
PAK pili-


065E08
5127092
PAK pili-


065E10
1907290
PAK pili-


065E11
4901855
PAK pili-


065F01
3307955
PAK pili-


065F02
4065383
PAK pili-


065F03
146511
PAK pili-


065F04
5204674
PAK pili-


065F06
5677927
PAK pili-


065F07
225606
PAK pili-


065F09
4131954
PAK pili-


065F12
3047361
PAK pili-


065G02
3201028
PAK pili-


065G03
3798133
PAK pili-


065G04
3442846
PAK pili-


065G05
4543237
PAK pili-


065G06
320024
PAK pili-


065G08
5093588
PAK pili-


065G09
3748272
PAK pili-


065G10
5888031
PAK pili-


065H01
395060
PAK pili-


065H02
1234143
PAK pili-


065H03
4282511
PAK pili-


065H04
1449253
PAK pili-


065H05
631397
PAK pili-


065H07
959444
PAK pili-


065H08
44580
PAK pili-


065H09
4188992
PAK pili-


065H10
5252649
PAK pili-


066A01
639405
PAK


066A02
950972
PAK


066A03
4096910
PAK


066A04
792936
PAK


066A05
2853998
PAK


066A06
954708
PAK


066A07
5528278
PAK


066A08
4717155
PAK


066A09
870436
PAK


066A10
4514642
PAK


066B01
3373489
PAK


066B02
6262256
PAK


066B03
3855210
PAK


066B04
861347
PAK


066B05
341365
PAK


066B09
1971103
PAK


066B10
3067544
PAK


066B11
1861028
PAK


066B12
811628
PAK


066C01
5134066
PAK


066C02
1400578
PAK


066C04
3408085
PAK


066C05
1152994
PAK


066C06
2712094
PAK


066C07
1098422
PAK


066C08
5538458
PAK


066C09
444477
PAK


066C11
3148189
PAK


066D01
6010854
PAK


066D03
5758451
PAK


066D04
235886
PAK


066D05
3156353
PAK


066D06
1878760
PAK


066D07
2930757
PAK


066D08
2263071
PAK


066D09
3586340
PAK


066D10
907398
PAK


066E01
5203283
PAK


066E02
4739343
PAK


066E03
962214
PAK


066E04
935502
PAK


066E05
6132671
PAK


066E07
5169822
PAK


086E08
3569363
PAK


066E09
5511249
PAK


066E10
25126
PAK


066E11
542926
PAK


066E12
4162302
PAK


066F02
4551124
PAK


066F03
1658622
PAK


066F04
759967
PAK


066F05
3965632
PAK


066F08
4910253
PAK


066F09
4210502
PAK


066F10
3672579
PAK


066F11
808137
PAK


066F12
475140
PAK


066G01
2269385
PAK


066G03
1480746
PAK


066G04
962539
PAK


066G07
734085
PAK


066G08
3679268
PAK


066G09
582812
PAK


066G10
396335
PAK


066G11
3241494
PAK


066H01
1807080
PAK


066H02
3397995
PAK


066H03
1649594
PAK


066H04
1632001
PAK


066H05
1375100
PAK


066H06
3908428
PAK


066H09
372279
PAK


066H11
395319
PAK


068A02
2094770
PAK pili-


068A04
1987268
PAK pili-


068A05
5740235
PAK pili-


068A06
3932206
PAK pili-


068A07
1660607
PAK pili-


068A08
1987270
PAK pili-


068A09
3926324
PAK pili-


068A11
3590093
PAK pili-


068A12
6120297
PAK pili-


068B01
1987268
PAK pili-


068B02
5417934
PAK pili-


068B04
556328
PAK pili-


068B05
5381209
PAK pili-


068B06
644690
PAK pili-


068B07
2901069
PAK pili-


068B08
3180329
PAK pili-


068B09
4547441
PAK pili-


068B11
3560647
PAK pili-


068B12
1373422
PAK pili-


068C02
4114885
PAK pili-


068C03
4508483
PAK pili-


068C04
339410
PAK pili-


068C05
5998779
PAK pili-


068C06
1438639
PAK pili-


068C07
5547182
PAK pili-


068C08
181598
PAK pili-


068C09
4347499
PAK pili-


068C10
4643796
PAK pili-


068C11
3382613
PAK pili-


068C12
6126369
PAK pili-


068D01
6112363
PAK pili-


068D02
103219
PAK pili-


068D03
947985
PAK pili-


068D05
3835199
PAK pili-


068D06
5370063
PAK pili-


068D07
3997066
PAK pili-


068D08
1347931
PAK pili-


068D09
1609368
PAK pili-


066D10
1934449
PAK pili-


068D11
5861335
PAK pili-


068D12
4010436
PAK pili-


068E03
147253
PAK pili-


068E04
5320966
PAK pili-


068E05
1753944
PAK pili-


068E06
1995183
PAK pili-


068E07
4306674
PAK pili-


068E08
3511207
PAK pili-


068E10
1137751
PAK pili-


068E11
4314936
PAK pili-


066F01
3355326
PAK pili-


068F02
5770189
PAK pili-


068F03
1345134
PAK pili-


068F05
1090425
PAK pili-


068F06
2216541
PAK pili-


068F07
494263
PAK pili-


068F08
4937550
PAK pili-


068F09
2079135
PAK pili-


068F10
3237043
PAK pili-


068F11
1366071
PAK pili-


068F12
257671
PAK pili-


068G01
503796
PAK pili-


068G02
4024172
PAK pili-


068G03
720922
PAK pili-


068G04
3520511
PAK pili-


068G06
1915614
PAK pili-


068G07
3056501
PAK pili-


068G09
1422135
PAK pili-


068G10
679204
PAK pili-


068G12
1235181
PAK pili-


068H01
1387944
PAK pili-


068H04
129130
PAK pili-


068H05
4432765
PAK pili-


068H06
5980173
PAK pili-


068H07
4459209
PAK pili-


068H08
281129
PAK pili-


068H09
3280854
PAK pili-


068H10
4419706
PAK pili-


068H11
395318
PAK pili-


069A02
1733608
PAK pili-


069A04
968280
PAK pili-


069A05
2017230
PAK pili-


069A06
4393279
PAK pili-


069A07
1992916
PAK pili-


069A08
3398642
PAK pili-


069A09
5742954
PAK pili-


069A10
907682
PAK pili-


069B02
6224406
PAK pili-


069B03
4325192
PAK pili-


069B04
5677171
PAK pili-


069B05
375214
PAK pili-


069B06
4099483
PAK pili-


069B07
2344645
PAK pili-


069B08
4300487
PAK pili-


069B10
2505909
PAK pili-


069B11
795009
PAK pili-


069B12
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PAK pili-


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PAK pili-


069C02
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PAK pili-


069C03
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PAK pili-


069C05
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PAK pili-


069C06
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PAK pili-


069C07
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PAK pili-


069C08
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PAK pili-


069C09
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PAK pili-


069C10
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PAK pili-


069C11
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PAK pili-


069D01
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PAK pili-


069D02
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PAK pili-


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PAK pili-


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PAK pili-


069D05
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PAK pili-


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PAK pili-


069D07
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PAK pili-


069D08
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PAK pili-


069D09
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PAK pili-


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PAK pili-


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PAK pili-


069D12
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PAK pili-


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PAK pili-


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PAK pili-


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PAK pili-


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PAK pili-


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PAK pili-


069E06
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PAK pili-


069E07
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PAK pili-


069E08
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PAK pili-


069E09
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PAK pili-


069E10
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PAK pili-


069E11
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PAK pili-


069E12
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PAK pili-


069F01
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PAK pili-


069F03
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PAK pili-


069F04
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PAK pili-


069F05
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PAK pili-


069F06
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PAK pili-


069F07
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PAK pili-


069F08
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PAK pili-


069F09
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PAK pili-


069F10
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PAK pili-


069F11
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PAK pili-


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PAK pili-


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PAK pili-


069G04
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PAK pili-


069G05
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PAK pili-


069G06
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PAK pili-


069G07
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PAK pili-


069G08
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PAK pili-


069G09
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PAK pili-


069G10
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PAK pili-


069G11
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PAK pili-


069G12
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PAK pili-


069H01
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PAK pili-


069H02
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PAK pili-


069H04
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PAK pili-


069H05
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PAK pili-


069H06
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PAK pili-


069H07
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PAK pili-


069H08
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PAK pili-


069H09
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PAK pili-


069H10
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PAK pili-


069H11
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PAK pili-


070A01
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PAK pili-


070A02
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PAK pili-


070A04
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PAK pili-


070A05
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PAK pili-


070A06
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PAK pili-


070A07
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PAK pili-


070A08
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PAK pili-


070A09
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PAK pili-


070A10
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PAK pili-


070A11
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PAK pili-


070A12
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PAK pili-


070B01
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PAK pili-


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PAK pili-


070B04
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PAK pili-


070B05
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PAK pili-


070B06
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PAK pili-


070B07
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PAK pili-


070B08
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PAK pili-


070B09
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PAK pili-


070B10
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PAK pili-


070B11
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PAK pili-


070B12
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PAK pili-


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PAK pili-


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PAK pili-


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PAK pili-


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PAK pili-


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PAK pili-


070C07
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PAK pili-


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PAK pili-


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PAK pili-


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PAK pili-


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PAK pili-


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PAK pili-


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PAK pili-


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PAK pili-


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PAK pili-


070D04
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PAK pili-


070D05
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PAK pili-


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PAK pili-


070D07
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PAK pili-


070D09
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PAK pili-


070D10
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PAK pili-


070D11
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PAK pili-


070D12
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PAK pili-


070E01
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PAK pili-


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PAK pili-


070E03
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PAK pili-


070E04
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PAK pili-


070E05
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PAK pili-


070E06
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PAK pili-


070E07
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PAK pili-


070E08
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PAK pili-


070E09
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PAK pili-


070E10
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PAK pili-


070E11
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PAK pili-


070F01
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PAK pili-


070F02
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PAK pili-


070F03
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PAK pili-


070F04
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PAK pili-


070F05
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PAK pili-


070F06
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PAK pili-


070F08
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PAK pili-


070F09
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PAK pili-


070F10
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PAK pili-


070F11
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PAK pili-


070F12
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PAK pili-


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PAK pili-


070G05
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PAK pili-


070G08
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PAK pili-


070G09
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PAK pili-


070G10
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PAK pili-


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PAK pili-


070G12
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PAK pili-


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PAK pili-


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PAK pili-


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PAK pili-


070H04
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PAK pili-


070H05
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PAK pili-


070H06
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PAK pili-


070H07
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PAK pili-


070H08
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PAK pili-


070H09
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PAK pili-


070H10
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PAK pili-


070H11
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PAK pili-


071A01
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PAK pili-


071A02
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PAK pili-


071A03
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PAK pili-


071A04
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PAK pili-


071A05
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PAK pili-


071A07
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PAK pili-


071A08
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PAK pili-


071A09
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PAK pili-


071A10
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PAK pili-


071A11
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PAK pili-


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PAK pili-


071B03
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PAK pili-


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PAK pili-


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PAK pili-


071B10
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PAK pili-


071B11
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PAK pili-


071B12
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PAK pili-


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PAK pili-


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PAK pili-


071C03
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PAK pili-


071C04
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PAK pili-


071C05
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PAK pili-


071C07
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PAK pili-


071C08
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PAK pili-


071C09
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PAK pili-


071C10
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PAK pili-


071C11
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PAK pili-


071C12
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PAK pili-


071D01
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PAK pili-


071D02
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PAK pili-


071D05
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PAK pili-


071D06
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PAK pili-


071D08
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PAK pili-


071D09
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PAK pili-


071D10
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PAK pili-


071D11
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PAK pili-


071E01
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PAK pili-


071E04
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PAK pili-


071E05
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PAK pili-


071E06
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PAK pili-


071E07
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PAK pili-


071E08
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PAK pili-


071E10
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PAK pili-


071E11
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PAK pili-


071E12
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PAK pili-


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PAK pili-


071F02
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PAK pili-


071F03
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PAK pili-


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PAK pili-


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PAK pili-


071F06
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PAK pili-


071F10
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PAK pili-


071F12
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PAK pili-


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PAK pili-


071G03
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PAK pili-


071G04
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PAK pili-


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PAK pili-


071G07
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PAK pili-


071G08
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PAK pili-


071G09
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PAK pili-


071G11
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PAK pili-


071G12
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PAK pili-


071H01
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PAK pili-


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PAK pili-


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PAK pili-


071H05
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PAK pili-


071H06
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PAK pili-


071H07
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PAK pili-


071H08
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PAK pili-


071H11
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PAK pili-


072A01
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PAK


072A02
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PAK


072A03
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PAK


072A04
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PAK


072A05
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PAK


072A07
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PAK


072A09
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PAK


072A10
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PAK


072A11
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PAK


072A12
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PAK


072B01
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PAK


072B02
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PAK


072B03
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PAK


072B04
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PAK


072B05
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PAK


072B06
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PAK


072B08
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PAK


072B10
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PAK


072B11
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PAK


072B12
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PAK


072C01
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PAK


072C02
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PAK


072C03
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PAK


072C04
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PAK


072C06
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PAK


072C07
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PAK


072C08
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PAK


072C09
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PAK


072C11
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PAK


072C12
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PAK


072D01
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PAK


072D02
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PAK


072D03
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PAK


072004
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PAK


072005
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PAK


072D06
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PAK


072D08
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PAK


072D09
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PAK


072D11
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PAK


072E01
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PAK


072E02
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PAK


072E03
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PAK


072E04
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PAK


072E05
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PAK


072E06
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PAK


072E07
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PAK


072E08
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PAK


072E09
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PAK


072E10
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PAK


072E11
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PAK


072E12
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PAK


072F01
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PAK


072F02
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PAK


072F03
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PAK


072F04
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PAK


072F05
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PAK


072F06
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PAK


072F07
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PAK


072F08
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PAK


072F09
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PAK


072F10
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PAK


072F11
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PAK


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PAK


072G02
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PAK


072G04
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PAK


072G05
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PAK


072G07
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PAK


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PAK


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PAK


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PAK


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PAK


072H02
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PAK


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PAK


072H05
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PAK


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PAK


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PAK


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PAK


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PAK


072H10
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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


073C11
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PAK


073C12
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PAK


073D01
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PAK


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PAK


073D03
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PAK


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PAK


073D05
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PAK


073D06
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PAK


073D07
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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


073E02
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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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494507
PAK


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4834488
PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


074A04
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PAK


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PAK


074A06
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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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1034469
PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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395319
PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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PAK


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1142928
PAK


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PAK


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PAK


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PAK


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PAK


076E09
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PAK


076E10
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PAK


076E11
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PAK


076E12
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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA001


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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546268
PA01


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PA01


213E01
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PA01


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PA01


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PA01


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817116
PA01


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1304734
PA01


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3288834
PA01


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6129947
PA01


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5431715
PA01


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5781283
PA01


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5094530
PA01


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PA01


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PA01


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409737
PA01


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65418
PA01


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PA01


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PA01


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621214
PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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PA01


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5318004
PA01


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5649851
PA01


213H01
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PA01


213H02
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PA01


213H03
204224
PA01


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PA01


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PA01


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PA01


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PA01


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492126
PA01


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288426
PA01


214A01
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PA01


214A02
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PA01


214A03
6178520
PA01


214A04
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PA01


214A05
1530709
PA01


214A06
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PA01


214A07
2029012
PA01


214A09
4531369
PA01


214A10
431629
PA01


214A12
306705
PA01


214B01
55431
PA01


214B02
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PA01


214B05
1354643
PA01


214B07
4204238
PA01


214B08
3510655
PA01


214B09
5424122
PA01


214811
1926174
PA01


214B12
466457
PA01


214C01
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PA01


214C02
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PA01


214C03
1079350
PA01


214C05
1428841
PA01


214C06
2705053
PA01


214C12
2726106
PA01


214D01
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PA01


214D04
2943719
PA01


214D05
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PA01


214D06
1833458
PA01


214D07
4199791
PA01


214D08
4403888
PA01


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2343237
PA01


214E01
931505
PA01


214E03
3442739
PA01


214E05
5979223
PA01


214E06
5979223
PA01


214E07
3704676
PA01


214E08
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PA01


214E09
937742
PA01


214E10
2215587
PA01


214E11
398190
PA01


214F01
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PA01


214F02
3374109
PA01


214F03
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PA01


214F04
4553579
PA01


214F05
223060
PA01


214F06
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PA01


214F07
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PA01


214F09
2641137
PA01


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2719501
PA01


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2712102
PA01


214G06
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PA01


214G07
326372
PA01


214G08
2147214
PA01


214G09
800299
PA01


214G10
1874570
PA01


214G11
2477596
PA01


214G12
552448
PA01


215A01
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PA01


215A03
1403774
PA01


215A10
359584
PA01


215B01
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PA01


215B04
4034019
PA01


215B05
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PA01


215B06
4839271
PA01


215B07
4155066
PA01


215B08
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PA01


215B09
546269
PA01


215D02
1551037
PA01


215D11
1078823
PA01


215E02
3204160
PA01


215E03
3929603
PA01


215E04
3397911
PA01


215E12
4313378
PA01


215F04
2345224
PA01


215F11
3169709
PA01


215G02
1657081
PA01


215G03
1776864
PA01


215G07
1428659
PA01


215H02
4492082
PA01


215H03
3712733
PA01


215H04
2007205
PA01


215H08
1995877
PA01


216A08
1070675
PA01


216A11
481393
PA01


216B08
6198757
PA01


216B11
3358655
PA01


216B12
2990462
PA01


216C03
5056159
PA01


216C05
866792
PA01


216C10
4420322
PA01


216D05
6087728
PA01


216D07
2116304
PA01


216D09
3201319
PA01


216G05
1117230
PA01


216G06
3870651
PA01


216H03
1045876
PA01


216H07
1526024
PA01


217A02
5270098
PA01


217A03
481393
PA01


217A09
661234
PA01


217B05
5263318
PA01


217B06
5968489
PA01


217B08
5390024
PA01


217B10
5697208
PA01


217B12
2333500
PA01


217C04
2012771
PA01


217C05
4149020
PA01


217C07
546268
PA01


217C09
546268
PA01


217C10
546270
PA01


217C11
546268
PA01


217D02
1286664
PA01


217D06
546268
PA01


217D07
1289165
PA01


217D08
546268
PA01


217E01
4251879
PA01


217F01
5646692
PA01


217F02
1687894
PA01


217F05
546271
PA01


217F07
338950
PA01


217F09
2506126
PA01


217F11
3390739
PA01


217F12
3390740
PA01


217G05
6012265
PA01


217G06
885011
PA01


217G07
546268
PA01


217G09
1146734
PA01


217G11
3515481
PA01


217H02
546269
PA01


217H04
4031786
PA01


217H05
3891961
PA01


217H06
5768037
PA01


217H08
546268
PA01


217H11
3553452
PA01


218A01
954087
PA01


218A02
628202
PA01


218A03
3809683
PA01


218A04
197279
PA01


218A05
5568853
PA01


218A06
4910637
PA01


218A08
5217883
PA01


218A09
4492177
PA01


218A10
1830069
PA01


218A11
4257084
PA01


218A12
65418
PA01


218B01
4144351
PA01


218B03
767461
PA01


218B05
436240
PA01


218B06
436240
PA01


218B07
2173490
PA01


218B08
2173490
PA01


218B10
5273292
PA01


218B12
5147713
PA01


218C02
307866
PA01


218C03
492126
PA01


218C05
2453351
PA01


218C06
4704214
PA01


218C07
371914
PA01


218C08
2408226
PA01


218C11
6228869
PA01


218C12
1046253
PA01


218D02
297517
PA01


218D04
297519
PA01


218D06
3725010
PA01


218D07
1985278
PA01


218D08
999927
PA01


218D09
3192085
PA01


218D10
4284004
PA01


218D11
3707859
PA01


218E01
3627888
PA01


218E02
5980173
PA01


218E03
2963758
PA01


218E07
3578842
PA01


218E08
946484
PA01


218E10
1064932
PA01


218E11
683870
PA01


218E12
4748413
PA01


218F02
3813551
PA01


218F03
339460
PA01


218F04
5982276
PA01


218F05
5142000
PA01


218F06
2023760
PA01


218F07
4275578
PA01


218F08
6122079
PA01


218F09
565522
PA01


218F10
4314876
PA01


218F11
5147705
PA01


218G01
1690213
PA01


218G02
6227025
PA01


218G03
4990664
PA01


218G06
1809683
PA01


218G07
1429084
PA01


218G08
125185
PA01


218G09
5944773
PA01


218G10
142140
PA01


218H01
374860
PA01


218H03
4902111
PA01


218H05
338950
PA01


218H06
4835152
PA01


218H07
4835152
PA01


218H08
253551
PA01


218H11
768212
PA01


219A01
3954605
PA01


219A02
2124983
PA01


219A03
1018388
PA01


219A04
894630
PA01


219A09
6189403
PA01


219A10
1427357
PA01


219B02
4675165
PA01


219B03
4612833
PA01


219B04
2959606
PA01


219B05
5500125
PA01


219B06
5163272
PA01


219B07
739442
PA01


219B10
1186050
PA01


219B11
1354643
PA01


219C01
5807299
PA01


219C04
5842394
PA01


219C05
1428659
PA01


219C07
147329
PA01


219C09
3659896
PA01


219C11
4299389
PA01


219D02
1717810
PA01


219D03
2375365
PA01


219D04
363632
PA01


219D05
5157544
PA01


219D06
5256933
PA01


219D09
912492
PA01


219D10
3209115
PA01


219D12
229062
PA01


219E01
3643734
PA01


219E04
807180
PA01


219E05
5497561
PA01


219E06
4623728
PA01


219E08
5181233
PA01


219E09
5280699
PA01


219E10
1513243
PA01


219E11
5694210
PA01


219E12
874289
PA01


219F03
6192289
PA01


219F04
5373424
PA01


219F05
2544966
PA01


219F06
1669748
PA01


219F08
2747845
PA01


219F10
1535896
PA01


219F11
1597361
PA01


219F12
51924
PA01


219G01
3341291
PA01


219G02
5980173
PA01


219G04
2780079
PA01


219G06
1260624
PA01


219G08
5807299
PA01


219G11
621219
PA01


219G12
2341527
PA01


219H02
3748607
PA01


219H05
5254106
PA01


219H09
4864670
PA01


219H10
4605059
PA01


219H11
3578842
PA01


221A03
5165608
PA01


221A04
3616674
PA01


221A05
3616674
PA01


221A09
4194427
PA01


221A10
5697208
PA01


221A11
906144
PA01


221B02
1128863
PA01


221B04
5005306
PA01


221B07
5807299
PA01


221B08
389138
PA01


221B09
1535898
PA01


221B10
1524451
PA01


221C01
1351298
PA01


221C02
1428659
PA01


221C07
2780079
PA01


221C09
6147917
PA01


221D02
1876783
PA01


221D03
441618
PA01


221D04
114208
PA01


221D05
1927015
PA01


221D06
1927015
PA01


221D07
389138
PA01


221D08
4284004
PA01


221D09
2129299
PA01


221D10
2816137
PA01


221D11
6017696
PA01


221D12
1954769
PA01


221E01
3149421
PA01


221E02
1954769
PA01


221E03
397111
PA01


221E04
295826
PA01


221E05
1756716
PA01


221E06
2345225
PA01


221E07
1028922
PA01


221E08
4665321
PA01


221E09
1258980
PA01


221E10
4911294
PA01


221F02
5807299
PA01


221F03
1412674
PA01


221F04
5222012
PA01


221F05
5793067
PA01


221F06
1948242
PA01


221F08
2253537
PA01


221G02
54536
PA01


221G03
2282835
PA01


221G04
5659898
PA01


221G0S
3522383
PA01


221G06
5868602
PA01


221G08
3659896
PA01


221G11
3659896
PA01


221H01
4558862
PA01


221H02
6215271
PA01


221H04
1037317
PA01


221H05
6075274
PA01


221H07
3146923
PA01


221H08
5551711
PA01


221H09
1383796
PA01


221H10
2849807
PA01


221H11
1164569
PA01


222A05
5254049
PA01


222A11
1064475
PA01


222B01
3578842
PA01


222B08
6160886
PA01


222C01
4866959
PA01


222C06
2849701
PA01


222C08
2165361
PA01


222E12
4790295
PA01


222F05
5272676
PA01


222F11
5676227
PA01


222G07
1426101
PA01


222H09
3456266
PA01


223A02
5905666
PA01


223A03
1044464
PA01


223A08
5242954
PA01


223A09
800304
PA01


223A11
4194332
PA01


223A12
973842
PA01


223B01
2022761
PA01


223B03
1832265
PA01


223B05
3876264
PA01


223B07
5069695
PA01


223B11
4194332
PA01


223C03
3239117
PA01


223C04
5263348
PA01


223C05
3848409
PA01


223C08
556544
PA01


223C11
6055515
PA01


223C12
6168358
PA01


223D03
3916604
PA01


223D06
503879
PA01


223D07
4280522
PA01


223D08
5123935
PA01


223D09
3219768
PA01


223D10
3293888
PA01


223D12
899039
PA01


223E01
3926495
PA01


223E02
4144783
PA01


223E03
340386
PA01


223E05
1354641
PA01


223E06
4501879
PA01


223E07
1906891
PA01


223E08
2471654
PA01


223E09
4845087
PA01


223E10
5155159
PA01


223E11
5155159
PA01


223E12
4585465
PA01


223F01
2428896
PA01


223F02
1289165
PA01


223F03
2375364
PA01


223F04
5913087
PA01


223F05
5173878
PA01


223F06
5967018
PA01


223F07
5967026
PA01


223F09
3472893
PA01


223F10
6122079
PA01


223F11
2692097
PA01


223F12
1103071
PA01


223G01
4627085
PA01


223G04
1195802
PA01


223G05
5171632
PA01


223G07
5632974
PA01


223G08
3627888
PA01


223G09
4494640
PA01


223G10
1906139
PA01


223G12
552448
PA01


223H03
876432
PA01


223H05
2930684
PA01


223H06
5930686
PA01


223H08
4016150
PA01


223H10
170395
PA01


225A02
1652817
PA01


225A03
247511
PA01


225A05
3809627
PA01


225A10
1364483
PA01


A1
3398642
PAK


A2
3379723
PAK


A3
2791021
PAK


A4
2715492
PAK


A5
2733396
PAK


B4
659794
PAK


B6
3509503
PAK


BEMA01
5822687
PA01


BEMA02
1876791
PA01


BEMA03
4708706
PA01


BEMA04
1970426
PA01


BEMA05
1017919
PA01


BEMA06
5804328
PA01


BEMA07
1901425
PA01


BEMA09
1897874
PA01


BEMA11
5316153
PA01


BEMA12
1970426
PA01


BEMB04
3510219
PA01


BEMB05
518952
PA01


BEMB06
1522099
PA01


BEMB09
884859
PA01


BEMB10
1023901
PA01


BEMC01
2798272
PA01


BEMC09
5957696
PA01


BEMC10
5685243
PA01


BEMC11
1586817
PA01


C1
4583326
PAK


C4
3144781
PAK


D6
3509503
PAK


D1
4583326
PAK


D2
3509503
PAK


D4
4638260
PAK


D6
3144781
PAK


yq-tray-434
5707222
PAK


yq-tray-436
6154439
PAK


yq-tray-438
1725057
PAK


yq-tray-440
336321
PAK


yq-tray-441
3761498
PAK


yq-tray-445
5299919
PAK


yq-tray-509
3659364
PAK


yq-tray-510
5252933
PAK


yq-tray-512
1921018
PAK


yq-tray-514
157070
PAK


yq-tray-515
4788598
PAK


yq-tray-517
1051875
PAK


yq-tray-518
1051875
PAK


yq-tray-519
5617558
PAK


yq-tray-520
3593363
PAK


yq-tray-522
339721
PAK


yq-tray-523
456995
PAK


yq-tray-526
3947588
PAK


yq-tray-L2
772748
PAK


yq-tray-L4
974632
PAK


yq-tray-L6
4711864
PAK


yq-tube-423
6154439
PAK


yq-tube-425
6154439
PAK


yq-tube-426
1922890
PAK


yq-tube-427
455162
PAK


yq-tube-432
5429711
PAK


yq-tube-433
3551095
PAK


yq-tube-436
6154439
PAK


yq-tube-438
1725056
PAK


yq-tube-440
336321
PAK


yq-tube-441
3761498
PAK


yq-tube-443
2905443
PAK


yq-tube-445
5299920
PAK


yq-tube-509
3659364
PAK


yq-tube-510
5252933
PAK


yq-tube-511
5863244
PAK


yq-tube-512
1921018
PAK


yq-tube-514
157070
PAK


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4788598
PAK


yq-tube-518
1051874
PAK


yq-tube-520
3593364
PAK


yq-tube-521
4088804
PAK


yq-tube-522
339721
PAK


yq-tube-523
456995
PAK


yq-tube-525
420142
PAK


yq-tube-526
3947590
PAK


yq-tube-L2
772748
PAK


yq-tube-L4
974632
PAK


yq-tube-L5
842580
PAK


yq-tube-L6
4711864
PAK


yq001
346171
PAK


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5638088
PAK


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5010879
PAK


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4815201
PAK


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3440810
PAK


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4060566
PAK


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5621597
PAK


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5450213
PAK


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5852319
PAK


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5336484
PAK


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420422
PAK


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718708
PAK


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1051362
PAK


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1433889
PAK


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5304562
PAK


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346171
PAK


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563809
PAK


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5010879
PAK


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4815202
PAK


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3440810
PAK


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4060566
PAK


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562159
PAK


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5450214
PAK


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5852319
PAK


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5336483
PAK


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42042
PAK


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718708
PAK


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1051363
PAK


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1433889
PAK


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5304562
PAK


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4910942
PAK


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3158388
PAK


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5781323
PAK


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3462938
PAK


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4806787
PAK


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5254917
PAK


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879367
PAK


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3666061
PAK


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5682932
PAK


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4437930
PAK


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2355967
PAK


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1036633
PAK


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2310864
PAK


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3968
PAK


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5326359
PAK


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4787579
PAK


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3006981
PAK


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24632
PAK


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5197201
PAK


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17465
PAK


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1855301
PAK


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5376060
PAK


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5781323
PAK


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1868969
PAK


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2341355
PAK


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7607
PAK


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2668034
PAK


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6002335
PAK


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5045325
PAK


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136420
PAK


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450182
PAK


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5342602
PAK


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PAK


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6184207
PAK


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4540967
PAK


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6069286
PAK


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4863021
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5943943
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6l05445
PAK


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4922981
PAK


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5640098
PAK


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3573502
PAK


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3947134
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6014140
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4060078
PAK


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2738432
PAK


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3142555
PAK


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1349094
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5255164
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4939275
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6256002
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5303638
PAK


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5855552
PAK


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1355230
PAK


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6014340
PAK


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7211
PAK


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1725699
PAK


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4792140
PAK


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3525719
PAK


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3562829
PAK


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483336
PAK


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3948019
PAK


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3551530
PAK


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5674845
PAK


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6132273
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4218739
PAK


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5993718
PAK


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4904227
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5827382
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5232107
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4191195
PAK


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4281645
PAK


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4079776
PAK


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499212
PAK


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1445149
PAK


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1848577
PAK


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5617827
PAK


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3769518
PAK


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3324609
PAK


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4787523
PAK


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4314367
PAK


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274655
PAK


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4013122
PAK


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1091008
PAK


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5273651
PAK


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527365
PAK


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1050594
PAK


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5844719
PAK


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4790607
PAK


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2955955
PAK


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2605446
PAK


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6132505
PAK


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5764392
PAK


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467804
PAK


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5224478
PAK


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5943918
PAK


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4523197
PAK


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3418100
PAK


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3445426
PAK


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5209130
PAK


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365889
PAK


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5968499
PAK


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3879399
PAK


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5923053
PAK


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4998512
PAK


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4508569
PAK


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5781283
PAK


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756481
PAK


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6032525
PAK


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5301398
PAK


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6013215
PAK


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488500
PAK


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3474448
PAK


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3593527
PAK


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4831330
PAK


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6106545
PAK


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1600391
PAK


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3070088
PAK


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5638129
PAK


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450406
PAK


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4525467
PAK


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2913281
PAK


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1244951
PAK


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1748207
PAK


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4303927
PAK


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456035
PAK


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5342235
PAK


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3552017
PAK


yq198
1081709
PAK


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4860003
PAK


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608110
PAK


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5853213
PAK


yq203
6138043
PAK


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6138043
PAK


yq206
3190834
PAK


yq207
1227518
PAK


yq208
6077287
PAK


yq209
396394
PAK


yq210
1858593
PAK


yq212
1920624
PAK


yq213
5341642
PAK


yq214
4057373
PAK


yq216
5707528
PAK


yq217
4792484
PAK


yq218
3630984
PAK


yq219
3323901
PAK


yq220
5346101
PAK


yq221
4335938
PAK


yq223
395319
PAK


yq224
4790530
PAK


yq227
4799812
PAK


yq228
4525490
PAK


yq229
4158658
PAK


yq230
355575
PAK


yq231
1664781
PAK


yq232
5618190
PAK


yq233
4481541
PAK


yq236
4783201
PAK


yq237
3631841
PAK


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5279426
PAK


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80263
PAK


yq240
4060540
PAK


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5750274
PAK


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6136055
PAK


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457532
PAK


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5054238
PAK


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5340298
PAK


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5442141
PAK


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1752445
PAK


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26811
PAK


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472171
PAK


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5310020
PAK


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6258564
PAK


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3631270
PAK


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3986330
PAK


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1909905
PAK


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4961011
PAK


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5344886
PAK


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1794056
PAK


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5622663
PAK


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1920818
PAK


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448226
PAK


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5622870
PAK


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1848341
PAK


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1724204
PAK


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4985498
PAK


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1727594
PAK


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3173887
PAK


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20580
PAK


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4752054
PAK


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2059133
PAK


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6006278
PAK


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3122299
PAK


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4190985
PAK


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6260937
PAK


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PAK


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5677964
PAK


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4260408
PAK


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1824685
PAK


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1911391
PAK


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PAK


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5944595
PAK


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4522691
PAK


yq288
4191034
PAK


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1662859
PAK


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PAK


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3509945
PAK


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5457826
PAK


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4161674
PAK


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6218220
PAK


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4909720
PAK


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3242506
PAK


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4785423
PAK


yq300
1053171
PAK


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3481634
PAK


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3604968
PAK


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1848611
PAK


yq304
5556783
PAK


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2994123
PAK


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532805
PAK


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4909720
PAK


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PAK


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2183791
PAK


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514649
PAK


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514649
PAK


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2922983
PAK


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3938305
PAK


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3008585
PAK


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PAK


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1955778
PAK


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2060699
PAK


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4476464
PAK


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1683461
PAK


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453170
PAK


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328420
PAK


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4816371
PAK


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5551527
PAK


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5408952
PAK


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3656220
PAK


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6246268
PAK


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5689845
PAK


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3129643
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4942834
PAK


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4962990
PAK


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3593373
PAK


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4862188
PAK


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4475236
PAK


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5687238
PAK


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PAK


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420070
PAK


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5254986
PAK


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404488
PAK


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PAK


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3364174
PAK


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420046
PAK


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1554758
PAK


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2178380
PAK


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5642385
PAK


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1051695
PAK


yq370
483080
PAK


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1954705
PAK


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1725290
PAK


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398646
PAK


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241422
PAK


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3415649
PAK


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2169080
PAK


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4248879
PAK


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4016636
PAK


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804155
PAK


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3230
PAK


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482768
PAK


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5707528
PAK


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5327307
PAK


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2046
PAK


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5637883
PAK


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2227022
PAK


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1831923
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5208464
PAK


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5918375
PAK


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4248933
PAK


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1751917
PAK


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510423
PAK


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514693
PAK


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5827390
PAK


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2934612
PAK


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2672028
PAK


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5254098
PAK


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3593339
PAK


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3593640
PAK


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636054
PAK


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456578
PAK


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3947139
PAK


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4792319
PAK


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6033032
PAK


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4535117
PAK


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473367
PAK


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6007245
PAK


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3324453
PAK


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4801907
PAK


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6013292
PAK


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600770
PAK


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4478003
PAK


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6154439
PAK


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5429711
PAK


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336321
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3761499
PAK


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457460
PAK


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1954013
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6200072
PAK


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5694746
PAK


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1501881
PAK


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1380923
PAK


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833533
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3415145
PAK


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3415145
PAK


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6033567
PAK


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1834663
PAK


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482451
PAK


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615716
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5623696
PAK


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4466909
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615716
PAK


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5617195
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6184599
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5694899
PAK


yq490
5616691
PAK


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5855086
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3949423
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474372
PAK


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718241
PAK


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1349427
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273258
PAK


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5859288
PAK


yq499
4274525
PAK


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6181080
PAK


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5415806
PAK


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5707622
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4273277
PAK


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4862384
PAK


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5530108
PAK


yq528
6083751
PAK


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455290
PAK


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3606825
PAK


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1981576
PAK


yq540
839186
PAK


yq541
4861418
PAK


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6007715
PAK


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3281356
PAK


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5694889
PAK


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3554932
PAK


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4819920
PAK


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4791519
PAK


yq551
5260804
PAK


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4801971
PAK


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642573
PAK


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4317166
PAK


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3324609
PAK


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4800242
PAK


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5197173
PAK


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5253316
PAK


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555662
PAK


yq564
5922452
PAK


yq568
4804815
PAK


yq569
4807928
PAK


yq570
4261077
PAK


yq571
1719155
PAK


yq572
4988719
PAK


yq574
3324900
PAK


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4536660
PAK


yq576
419363
PAK


yq579
5849545
PAK


yq580
456046
PAK


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855748
PAK


yq582
1690865
PAK


yq583
5991336
PAK


yq584
5853904
PAK


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5694892
PAK


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5484510
PAK


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454274
PAK


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5788824
PAK


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5857361
PAK


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5707319
PAK


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5916385
PAK


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42750780
PAK


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3936955
PAK


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3551821
PAK


yq597
5208616
PAK


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6132782
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yq602
4549080
PAK


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4383148
PAK


yq604
1424381
PAK


yq605
480240
PAK

## Claims

1. A method of screening for an antibacterial agent, comprising:
a step of contacting a test compound with an isolated Pseudomonas aeruginosa protein LpxC;
a further step of determining whether the test compound binds to the protein; and
a further step of determining whether the test compound has either bactericidal or bacteriostatic activity against Pseudomonas aeruginosa.

2. The method of claim 1 further comprising determining whether the test compound is active against the protein.

3. The method of claim 2 wherein determining whether the test compound is active comprises determining whether the test compound inhibits a biochemical pathway that involves the protein.

4. The method of claim 1 wherein determining whether the test compound has either bactericidal or bacteriostatic activity comprises determining whether the test compound suppresses the growth of a Pseudomonas aeruginosa bacterium comprising the protein.