Abstract:
Disclosed are various genes encoding proteins that are shown to play a role, direct or indirect, in microbial resistance of an organism in a biofilm and homologs thereof. Also disclosed are methods of identifying a compound that modulates microbial resistance of an organism in a biofilm, and methods of identifying genes that encode proteins that play a role, direct or indirect, in biofilm resistance.

Description:
REFERENCE TO RELATED APPLICATIONS  
       [0001]    This application claims priority from U.S. Provisional Application No. 60/323,241, filed Sep. 18, 2001, the entirety of which is incorporated by reference. 
     
    
     
       BACKGROUND OF THE INVENTION  
         [0002]    Biofilms are complex communities of microorganisms, comprised either of a single or multiple species. Over the past few decades, there has been a growing realization that bacteria in most environments are not found in a unicellular, planktonic existence such as those typically studied in the laboratory, but exist predominantly in multi-cellular surface attached communities called biofilms. This realization has spurred much research into the physical and chemical properties of biofilms, their morphology, and the mechanism of their development.  
           [0003]    The transition from the planktonic mode of existence to a biofilm is a regulated developmental process. This biofilm community has a number of distinct characteristics including the production of exopolysaccharides, the formation of chemical and pH gradients, a marked degree of structural heterogeneity, and the development of high level resistance to a variety of antimicrobial agents.  
           [0004]    It has been shown that biofilm grown cells can become 10-1000× more resistant to the effects of antimicrobial agents than their planktonic counterparts. This characteristic of biofilms makes them extremely difficult to control in both medical and industrial settings. Traditional antibiotic therapies can eliminate planktonic bacteria, but organisms growing in a biofilm survive treatment and can eventually regrow once antibiotics are discontinued. The levels of antibiotic required to eliminate biofilm bacteria often cannot be achieved in the patient or are toxic. Therefore, biofilm-based infections can become chronic with the only recourse being removal of the contaminated surface.  
           [0005]    The formation of biofilms can have serious negative consequences in medical, industrial, and natural settings, resulting in high costs both in human health and economic terms. Biofilm-associated infections extend hospital stays an average of about three days and it is estimated that up to 65% of nosocomial infections are biofilm-based with an associated treatment cost in excess of a billion dollars per year. In clinical settings, biofilms can form on a variety of surfaces. Biofilms formed on indwelling medical devices serve as a reservoir of bacteria that can be shed into the body, leading to a chronic systemic infection. Indeed, up to 82% of nosocomial bacteremias are the result of bacterial contamination of intravascular catheterizations. Examples of biofilms include oral microbes on teeth, chronic  Pseudomonas aeruginosa  infections in the lungs of cystic fibrosis patients and bacterial contaminants on medical devices such as pacemakers and catheters. Biofilms can form in almost any hydrated environment that has the proper nutrient conditions, and can develop on a wide variety of abiotic (both hydrophobic and hydrophilic) and biotic (e.g., eukaryotic cells) surfaces.  
           [0006]    The formation of biofilms is an important aspect of normal development for many microbial species. The mechanisms responsible for the increased biofilm resistance, however, are not well understood. It has been suggested that the exopolysaccharide matrix that surrounds the cells in the biofilm prevent diffusion of antimicrobial agents through the biofilm, thus preventing access of the agent to the cells. While this may be the case for some antimicrobial agents, for many others it has been shown that antimicrobial agents can penetrate the biofilm matrix but are still unable to kill cells in the biofilm. It has also been suggested that cells within the biofilm grow slowly in response to nutrient deprivation and perhaps some form of stress. Therefore, antimicrobial agents that only act on actively dividing bacterial cells would be non-functional in this sort of environment. While a number of studies support the idea that slowed growth rate can explain some aspects of biofilm-related resistance, other studies have suggested that the full extent of resistance cannot be accounted for by this mechanism. Finally, while it has been suggested that quorum sensing is involved in resistance to antimicrobial agents, it is not clear what role, if any, this system plays in biofilm-related antimicrobial resistance. To date, none of the models put forward adequately explain the level of resistance to biocides attained by cells in a biofilm.  
           [0007]    There is emerging evidence that the transition from planktonically growing bacteria to life in a biofilm requires a genetic program that responds to a variety of environmental cues. It is possible that the development of biofilm-related antibiotic resistance is also a regulated event, and taken together with the marked biochemical and physiological heterogeneity of biofilms, the induction of a biofilm-related resistance phenotype may occur within distinct regions of the biofilm. The subset of biocide-resistant cells in the biofilm is referred to as “persistors”. The term persistor refers to the fact that not all of the cells within the biofilm resist killing by antimicrobial agents resulting in the survival of a small population of very resistant cells after antibiotic treatment.  
           [0008]    There exists a strong need to discover methods and compositions that will inhibit biofilm formation and overcome their resistance mechanisms.  
         SUMMARY OF THE INVENTION  
         [0009]    The invention features method for identifying compounds that can alter, e.g., reduce the resistance of microbial cells growing in a biofilm to antimicrobial agents. Certain of the compounds may also be used reduce resistance to antimicrobial agents associated with other physiological states as well as resistance caused by genetic changes. The invention also features methods for identifying genes that play a role in biofilm resistance as well as certain such genes and the proteins they encode.  
           [0010]    A compound or compounds that are identified by the invention as modulating biofilm resistance to an antimicrobial agent can be further analyzed in the context of a flow cell assay and a colony biofilm assay. Using the flow cell assay, a biofilm, allowed to form in the flow cell, can be monitored in the presence of an antimicrobial agent and a compound. The antimicrobial agent and the compound can be quickly removed and the effect of the treatment on biofilm viability can be determined using standard techniques.  
           [0011]    A colony biofilm assay can also be utilized to test the effect of biofilm resistance to antimicrobial agents in the presence of compounds identified by the invention. Microorganisms are allowed to form a biofilm on a polycarbonate filter then transferred to solid media. The biofilm is exposed to an antimicrobial agent and a compound and tested for viability after a pre-determined amount of time. A biofilm treated with a compound identified by the invention will demonstrate reduced viability and/or increased sensitivity when exposed to the antimicrobial agent after or during exposure to the compound. These techniques are described in more detail below.  
           [0012]    The invention features a method of identifying a candidate compound for altering the sensitivity of a microorganism to an antimicrobial agent, the method comprising: a) providing a sample comprising an efflux pump selected from the group consisting of: i) an efflux pump comprising a polypeptide comprising SEQ ID NO:4 (gene PA1874), ii) an efflux pump comprising a polypeptide comprising SEQ ID NO: 12 (gene PA4142), iii) an efflux pump comprising a polypeptide comprising SEQ ID NO:18 (gene PA2389),  
           [0013]    b) contacting the sample with a test compound; and  
           [0014]    c) measuring activity of the efflux pump, wherein a change in the activity of the efflux pump in the presence of the test compound relative to the activity of the efflux pump in a control sample in the absence of the test compound, indicates that the compound is a candidate compound for altering the sensitivity of a microorganism to an antimicrobial agent.  
           [0015]    In various embodiments: the efflux pump comprising a polypeptide comprising SEQ ID NO:4 (gene PA1874), further comprises at least one of: a polypeptide comprising SEQ ID NO:6 (gene PA1875), a polypeptide comprising SEQ ID NO:8 (gene PA1876), and a polypeptide comprising SEQ ID NO:10 (gene PA1877); the efflux pump comprising a polypeptide comprising SEQ ID NO:12 (gene PA4142), further comprises at least one of: a polypeptide comprising SEQ ID NO:14 (gene PA4143), and a polypeptide comprising SEQ ID NO:16 (gene PA4144); and the efflux pump comprising a polypeptide comprising SEQ ID NO:18 (gene PA2389), further comprises at least one of: a polypeptide comprising SEQ ID NO:20 (gene PA2390), and a polypeptide comprising SEQ ID NO:22 (gene PA2391).  
           [0016]    The invention also features: a method of identifying a candidate compound for altering the sensitivity of a microorganism to an antimicrobial agent, the method comprising: a)  
           [0017]    providing a sample comprising a polypeptide selected from the group consisting of: i) a polypeptide comprising SEQ ID NO:8 (gene PA1876), ii) an efflux pump comprising a polypeptide comprising SEQ ID NO: 14 (gene PA4143), iii) an efflux pump comprising a polypeptide comprising SEQ ID NO:20 (gene PA2390),  
           [0018]    b) contacting the sample with a test compound; and  
           [0019]    c) measuring the ATPase activity of the polypeptide, wherein a change in the ATPase activity of the polypeptide in the presence of the test compound relative to the activity of the polypeptide in a control sample in the absence of the test compound, indicates that the compound is a candidate compound for altering the sensitivity of a microorganism to an antimicrobial agent.  
           [0020]    In various embodiments: the sample comprises cells expressing the polypeptide, the sample comprises cells harboring an expression vector encoding the polypeptide. The cells are grown in a biofilm, the cells are grown planktonically, the sample comprises vesicles containing the efflux pump or a membrane system containing the efflux pump; the method comprises measuring the activity of two or more efflux pumps selected from the group consisting of: i) an efflux pump comprising a polypeptide comprising SEQ ID NO:4 (gene PA1874), ii) an efflux pump comprising a polypeptide comprising SEQ ID NO: 12 (gene PA4142), and iii) an efflux pump comprising a polypeptide comprising SEQ ID NO:18 (gene PA2389).  
           [0021]    The invention further features: a method of identifying a candidate compound for altering the sensitivity of a microorganism to an antimicrobial agent, the method comprising:  
           [0022]    a) providing a sample comprising a glucosyltransferase polypeptide selected from the group consisting of: i) a polypeptide comprising SEQ ID NO:2 (gene PA1163), ii) a polypeptide comprising SEQ ID NO:27, iii) a polypeptide comprising SEQ ID NO:28, iv) a polypeptide comprising SEQ ID NO:29, and v) a polypeptide comprising SEQ ID NO:32,  
           [0023]    b) contacting the sample with a test compound; and  
           [0024]    c) measuring activity of the glucosyltransferase polypeptide, wherein a change in the activity of the glucosyltransferase polypeptide in the presence of the test compound relative to the activity of the glucosyltransferase polypeptide in a control sample in the absence of the test compound, indicates that the compound is a candidate compound for altering the sensitivity of a microorganism to an antimicrobial agent.  
           [0025]    In various embodiments: the glucosyltransferase polypeptide is contacted with the test compound in the presence of an antimicrobial agent; the sample comprises cells expressing the glucosyltransferase polypeptide; sample comprises cells harboring an expression vector encoding the glucosyltransferase polypeptide; the cells are grown as a biofilm; the cells are grown planktonically; and activity is measured by measuring cyclic-b-(1,3)-glucan formation.  
           [0026]    The invetion further features: a method of identifying a candidate compound for altering the sensitivity of a microoganism to an antimicrobial agent, the method comprising:  
           [0027]    a) providing a sample comprising cells expressing a gene encoding a glucosyltransferase polypeptide selected from the group consisting of: i) a polypeptide comprising SEQ ID NO:2 (gene PA1163), ii) a polypeptide comprising SEQ ID NO:27, iii) a polypeptide comprising SEQ ID NO:28, iv) a polypeptide comprising SEQ ID NO:29, and v) a polypeptide comprising SEQ ID NO:32,  
           [0028]    b) contacting the sample with a test compound; and  
           [0029]    c) measuring the expression of a gene encoding a glucosyltransferase polypeptide in the cells, wherein a change in the expression of the gene encoding the glucosyltransferase polypeptide in the presence of the test compound relative to the expression of the gene encoding the glucosyltransferase polypeptide in a control sample in the absence of the test compound, indicates that the compound is a candidate compound for altering the sensitivity of a microorganism to an antimicrobial agent.  
           [0030]    In various embodiments: the cells are contacted with the test compound in the presence of an antimicrobial agent; the expression of the gene is measured by measuring mRNA expression; expression of the gene is measured by measuring polypeptide expression; and the cells contacted with the test compound are growing as a biofilm.  
           [0031]    The invention also features: A method of identifying a candidate compound for altering the sensitivity of a microorganism to an antimicrobial agent, the method comprising:  
           [0032]    a) providing a sample of cells expressing an efflux pump selected from the group consisting of: i) an efflux pump comprising a polypeptide comprising SEQ ID NO: 4 (gene PA1874), ii) an efflux pump comprising a polypeptide comprising SEQ ID NO: 12 (gene PA4142), iii) an efflux pump comprising a polypeptide comprising SEQ ID NO: 18 (gene PA2389),  
           [0033]    b) contacting the cells with a test compound; and  
           [0034]    c) measuring expression of the efflux pump in the cells wherein a change in the expression of the efflux pump in the presence of the test compound relative to the expression of the efflux pump in a control sample in the absence of the test compound, indicates that the test compound is a candidate compound for altering the sensitivity of a microorganism to an antimicrobial agent.  
           [0035]    In various embodiments: the efflux pump comprising a polypeptide comprising SEQ ID NO: 4 (gene PA1874), further comprises at least one of: a polypeptide comprising SEQ ID NO:6 (gene PA1875), a polypeptide comprising SEQ ID NO:8 (gene PA1876), and a polypeptide comprising SEQ ID NO:10 (gene PA1877); the efflux pump comprising a polypeptide comprising SEQ ID NO:12 (gene PA4142), further comprises at least one of: a polypeptide comprising SEQ ID NO:14 (gene PA4143), and a polypeptide comprising SEQ ID NO:16 (gene PA4144); the efflux pump comprising a polypeptide comprising SEQ ID NO:18 (gene PA2389), further comprises at least one of: a polypeptide comprising SEQ ID NO:20 (gene PA2390), and a polypeptide comprising SEQ ID NO:22 (gene PA2391); the cells are contacted with the test compound in the presence of an antimicrobial agent; expression is measured by measuring polypeptide expression; expression is measured by measuring mRNA expression; the cells are grown as a biofilm; and the cells are grown planktonically.  
           [0036]    The invention also features: a purified polypeptide comprising an amino acid sequence selected from the group consisting of: SEQ ID NO:4 (gene PA1874), SEQ ID NO:6 (gene PA1875), SEQ ID NO:8 (gene PA1876), SEQ ID NO:10 (gene PA1877), SEQ ID NO:12 (gene PA4142), SEQ ID NO:14 (gene PA4143), SEQ ID NO:16 (gene PA4144), SEQ ID NO:18 (gene PA2389), SEQ ID NO:20 (gene PA2390), SEQ ID NO:22 (gene PA2391) and a purified polypeptide comprising the amino acid sequence selected from the group consisting of: SEQ ID NO:2 (gene PA1163), SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29 and SEQ ID NO:31.  
           [0037]    The invention includes a method of identifying a gene that functions in biofilm-related resistance to an antimicrobial agent, the method comprising:  
           [0038]    (a) providing a library of clones of a selected microbial strain that have been subjected to mutagenesis;  
           [0039]    (b) growing each of a plurality of clones from the library as a biofilm;  
           [0040]    (c) identifying a clone having altered biofilm-related resistance to the antimicrobial agent relative the to biofilm-related resistance of the selected microbial stain;  
           [0041]    (d) isolating from the identified clone a gene having a mutation.  
           [0042]    In various embodiments: the antimicrobial agent is an antibiotic; the mutagenesis comprises random mutagenesis; the selected strain exhibits at least a two-fold change in resistance to the anti-microbial agent; the microorganism is a bacterial microorganism; the microorganism is a fungal microorganism; the mutagenesis comprises chemical mutagenesis.  
           [0043]    The invention includes: a method of identifying a compound that increases the sensitivity of a microorganism to a selected antimicrobial agent, the method comprising:  
           [0044]    (a) providing a sample comprising a microorganism in a biofilm;  
           [0045]    (b) contacting the sample with a test compound and the selected antimicrobial agent; and  
           [0046]    (c) measuring the sensitivity of the microorganism in the sample to the selected antimicrobial agent, wherein an increase in the sensitivity of the microorganism to the selected antimicrobial agent relative to the sensitivity of the microorganism in a biofilm to the selected antimicrobial agent in the absence of the test compound indicates that the test compound is a compound that increases the sensitivity of microorganism in a biofilm to the selected antimicrobial agent.  
           [0047]    In various embodiments: the antimicrobial agent is selected from the group consisting of aminoglycosides, macrolides, tetracyclines, penicillins, β-lactam antibiotics (including cephalosporins, β-lactam/β-lactamase combinations), quinolones (including fluoroquinolones), glycopeptides, sulfonamides, sulfones, oxazolidinones, streptogramins; the microorganism is selected from the group consisting of  Pseudomonas fluorescens, Pseudomonas aeruginosa, Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Pseudomonas syringae, Pseudomonas aureofaciens, Pseudomonas fragi, Fusobacterium nucleatum, Treponema denticola, Porphyromonas gingivalis, Moraxella catarrhalis, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudo tuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis, Bordetella bronchiseptica, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Pasteurella multocida, Pasteurella haemolytica, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Borrelia burgdorferi, Vibrio cholerae, Vibrio paramaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Gardnerella vaginalis , Bacteroides spp.,  Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycrobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans , Streptococcus spp., Enterococcus spp., Desulfvibrio spp., Actinomyces spp., Erwinia spp., Xanthomonas spp., Xylella spp., Clavibacter spp., Desulfomonas spp., Desulfovibrio spp., Desulfococcus spp., Desulfobacter spp., Desulfobulbus spp., Desulfosarcina spp., Deslfuromonas spp., Bacillus spp., Streptomyces spp., Clostridium spp., Rhodococcus spp., Thermatoga spp., Sphingomonas spp., Zymomonas spp., Micrococcus spp., Azotobacter spp., Norcardia spp., Brevibacterium spp., Alcaligenes spp., Microbispora spp., Micromonospora spp.,  Methylobacterium organophilum, Pseudomonas reptilivora, Pseudomonas carragienovora, Pseudomonas dentificans , Corynebacterium spp., Propionibacterium spp., Xanothomonas spp., Methylobacterium spp., Chromobacterium spp., Saccharopolyspora spp., Actinobacillus spp., Alteromonas spp., Aeronomonas spp.,  Agrobacterium tumefaciens, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus warneri, Staphylococcus cohnii, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus lugdunensis, Staphlyococcus intermedius, Staphylococcus hyicus, Staphylococcus saccharolyticus  and Rhizobium spp; the biofilm is associated with an abiotic surface; the biofilm is associated with a biotic surface; the biofilm is not associated with a surface; the microorganism has a mutation that reduces the expression or activity of a polypeptide selected from the group consisting of: SEQ ID NO:4 (gene PA1874), SEQ ID NO:6 (gene PA1875), SEQ ID NO:8 (gene PA1876), SEQ ID NO:10 (gene PA 1877), SEQ ID NO:12 (gene PA4142), SEQ ID NO:14 (gene PA4143), SEQ ID NO:16 (gene PA4144), SEQ ID NO:18 (gene PA2389), SEQ ID NO:20 (gene PA2390), SEQ ID NO:22 (gene PA2391); and the microorganism has a mutation that reduces the expression or activity of a polypeptide selected from the group consisting of: SEQ ID NO:2 (gene PA1163), SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29 and SEQ ID NO:31 (e.g., a deletion mutation or an insertion mutation).  
           [0048]    The invention features a method of identifying a candidate compound for altering the sensitivity of a microoganism to an antimicrobial agent, the method comprising:  
           [0049]    a) providing a sample comprising cells harboring a reporter gene comprising a nucleotide sequence encoding a detectable protein operably linked to an expression control sequence comprising a nucleotide sequence selected from the group consisting of: i) SEQ ID NO:23 (expression control for PA1874), ii) SEQ ID NO:24 (expression control for PA4242), iii) SEQ ID NO:25 (expression control for PA2389), and iv) SEQ ID NO:26 (expression control for PA1163),  
           [0050]    b) measuring the expression of the reporter gene in the cells in the presence of a test compound, wherein a change in the expression of the reporter gene in the presence of the test compound relative to the expression of the reporter gene in a control sample in the absence of the test compound, indicates that the compound is a candidate compound for altering the sensitivity of a microorganism to an antimicrobial agent.  
           [0051]    In certain embodiments expression of the reporter gene is measured by measuring the expression of the detectable protein.  
           [0052]    The invention includes: a method of identifying a candidate compound for inhibiting the growth of a microorganism, the method comprising:  
           [0053]    a) providing a sample comprising an efflux pump selected from the group consisting of: i) an efflux pump comprising a polypeptide comprising an amino acid sequence at least 70% identical to SEQ ID NO:4 (gene PA1874), ii) an efflux pump comprising a polypeptide comprising an amino acid sequence at least 70% identical to SEQ ID NO: 12 (gene PA4142), iii) an efflux pump comprising a polypeptide comprising SEQ ID NO:18 (gene PA2389),  
           [0054]    b) contacting the sample with a test compound; and  
           [0055]    c) measuring activity of the efflux pump, wherein a change in the activity of the efflux pump in the presence of the test compound relative to the activity of the efflux pump in a control sample in the absence of the test compound, indicates that the compound is a candidate compound for inhibiting the growth of a microorganism.  
           [0056]    In certain embodiments: the efflux pump comprising a polypeptide comprising SEQ ID NO:4 (gene PA1874), further comprises at least one of: a polypeptide comprising SEQ ID NO:6 (gene PA1875), a polypeptide comprising SEQ ID NO:8 (gene PA1876), and a polypeptide comprising SEQ ID NO:10 (gene PA1877); the efflux pump comprising a polypeptide comprising SEQ ID NO:12 (gene PA4142), further comprises at least one of: a polypeptide comprising SEQ ID NO:14 (gene PA4143), and a polypeptide comprising SEQ ID NO:16 (gene PA4144).; the efflux pump comprising a polypeptide comprising SEQ ID NO:18 (gene PA2389), further comprises at least one of: a polypeptide comprising SEQ ID NO:20 (gene PA2390), and a polypeptide comprising SEQ ID NO:22 (gene PA2391); the sample comprises cells expressing the polypeptide; the cells are grown in a biofilm; and the cells are grown planktonially.  
           [0057]    The invention features: a method of identifying a candidate compound that inhibits growth of a microorganism, the method comprising:  
           [0058]    a) providing a sample comprising a glucosyltransferase polypeptide selected from the group consisting of: i) a polypeptide comprising SEQ ID NO:2 (gene PA1163), ii) a polypeptide comprising SEQ ID NO:27, iii) a polypeptide comprising SEQ ID NO:28, iv) a polypeptide comprising SEQ ID NO:29, and v) a polypeptide comprising SEQ ID NO:32,  
           [0059]    b) contacting the sample with a test compound; and  
           [0060]    c) measuring activity of the glucosyltransferase polypeptide, wherein a change in the activity of the glucosyltransferase polypeptide in the presence of the test compound relative to the activity of the glucosyltransferase polypeptide in a control sample in the absence of the test compound, indicates that the compound is a candidate compound inhibiting the growth of a microorganism.  
           [0061]    “Naturally-occurring” as used herein, as applied to an object, refers to the fact that an object can be found in nature. For example, a polypeptide or polynucleotide sequence that is present in an organism (including viruses) that can be isolated from a source in nature is naturally-occurring.  
           [0062]    By “compound,” “test compound,” or “candidate compound” we mean any substance or chemical. Encompassed within this definition are, for example, compound analogs, naturally occurring, synthetic and recombinant pharmaceuticals, hormones, or antimicrobials, antibiotics, nucleic acid molecules, polypeptides, and peptide nucleic acids.  
           [0063]    By “test sample” we mean one or more of the components of a sample and a test compound.  
           [0064]    By “control sample” we mean a test sample lacking a test compound. Therefore, the control sample has all of the characteristics of the test sample except for the presence of a test compound in the test sample.  
           [0065]    By “cell component” we mean a protein, carbohydrate, lipid, nucleic acid molecule, ion, or any other constituent contained within or secreted by an organism.  
           [0066]    By “biological activity” we mean a protein having structural, regulatory, or biochemical functions of a naturally occurring molecule.  
           [0067]    By “efflux pump” we mean a protein assembly which exports substrate molecules, compounds, or antimicrobial agents from the cytoplasm or periplasm of a cell, in an energy dependent fashion. Thus an efflux pump will typically be located in the cytoplasmic membrane of the cell (spanning the cytoplasmic membrane). For example, in Gram-negative bacteria the pump may span the periplasmic space and there may also be portion of the efflux pump which spans the outer membrane.  
           [0068]    “Expression cassette” refers to a recombinantly produced nucleic acid molecule which is capable of directing the expression of one or more proteins. The expression cassette must include a promoter capable of directing the expression of said protein(s), and a sequence encoding one or more proteins. Optionally, the expression cassette may include transcription termination, splice recognition, and polyadenylation addition sites. Desired promoters include the TK, CMV, MMTV, MoMLV, P tac , P lac , P ara , P xyl , and P T7  promoters. In addition, the expression cassette may contain a selectable marker, for example, Neo, SV2 Neo, hygromycin, phleomycin, histidinol, DHFR, tetracycline, carbenecillin, gentamycin, kanamycin, and ampicillin; a chemiluminescent marker, for example, luciferase and green fluorescent protein; or an enzymatic marker, for example, chloramphenicol acetyltransferase.  
           [0069]    “Reporter gene” means a gene that encodes a detectable protein, e.g., reporter enzyme, such as they are known in the art or are later developed, such as a reporter enzyme activity. A reporter gene may be a component of an expression cassette. “Reporter enzyme” means an enzyme that encode a reporter enzyme that has a detectable read-out, such as beta-lactamase, beta-galactosidase, or luciferase (for beta-lactamase, see WO 96/30540 to Tsien, published Oct. 3, 1996). Desirably, reporter enzymes localize in the cytosol of a cell, such as cytosolic beta-lactamase. Reporter enzymes can be detected using methods known in the art, such as the use of chromogenic or fluorogenic substrates for reporter enzymes as such substrates are known in the art. Such substrates are desirably membrane permeant. Chromogenic or fluorogenic readouts can be detected using, for example, optical methods such as absorbance or fluorescence. A reporter gene can be part of a reporter gene construct, such as a plasmid or viral vector, such as a retrovirus or adeno-associated virus. A reporter gene can also be extra-chromosomal or be integrated into the genome of a host cell. The expression of the reporter gene can be under the control of exogenous expression control sequences or expression control sequences within the genome of the host cell. Under the latter configuration, the reporter gene is desirably integrated into the genome of the host cell.  
           [0070]    “Polypeptide” means any chain of amino acids, regardless of length or post-translational modification (e.g., glycosylation or phosphorylation). By the use of “precursor” we mean that a polypeptide can be encoded by a full length gene sequence or by any portion of the coding sequence so long as the enzymatic activity is retained.  
           [0071]    “Substantially pure polypeptide” means a polypeptide which has been separated from components which naturally accompany it. Typically, the polypeptide is substantially pure when it is at least 60%, by weight, free from the proteins and naturally-occurring organic molecules with which it is naturally associated. It is desirable for the preparation to be at least 75%, more desirably at least 90%, and even more desirably 95%, and most desirably 99%, by weight the desired protein. A substantially pure polypeptide may be obtained, for example, by extraction from a natural source (e.g., a bacterial cell); by expression of a recombinant nucleic acid molecule encoding the polypeptide; or by chemically synthesizing the protein. Purification of polypeptides may be by techniques known in the art, for example, differential extraction, salt fractionation, chromatography on ion exchange resins, affinity chromatography, centrifugation, and the like. See, for example, Methods in Enzymology for a variety of methods for purifying proteins. Purity can be measured by any appropriate method, e.g., those described in column chromatography, polyacrylamide gel electrophoresis, or by HPLC analysis.  
           [0072]    A protein is substantially free of naturally associated components when it is separated from those contaminants which accompany it in its natural state. Thus a protein which is chemically synthesized or produced in a cellular system different from the cell from which it naturally originates will be substantially free from its naturally associated components. Accordingly, substantially pure polypeptides include those derived from prokaryotic organisms, but synthesized in other prokaryotes or eukaryotes.  
           [0073]    “Substantially pure DNA” means DNA that is free of the genes which, in the naturally occurring genome of the organism from which the DNA of the invention is derived, flank the gene. The term therefore includes, for example, a recombinant DNA which is incorporated into a vector; into an autonomously replicating plasmid or virus; or into the genomic DNA of a prokaryote or eukaryote; or which exists as a separate molecule (e.g., a cDNA or a genomic or cDNA fragment produced by PCR or restriction endonuclease digestion) independent of other sequences. It also includes a recombinant DNA which is part of a hybrid gene encoding additional polypeptide sequence.  
           [0074]    By “antimicrobial agent” we mean an agent, e.g., a compound which reduces the rate of growth of an organism compared to the rate of growth of the organism in the absence of the composition. A reduction in the rate of growth of an organism may be by at least 5%, more desirably, by at least 10%, even more desirably, by at least 20%, 50%, or 75%, and most desirably, by 90% or more. The definition also extends to compositions which affect the viability, virulence, or pathogenicity of an organism. An antimicrobial agent can be natural (e.g., derived from bacteria), synthetic, or recombinant. An antimicrobial agent can be bacteriostatic, bactericidal or both. An antimicrobial agent is bacteriostatic if it inhibits cell division without affecting the viability of the inhibited cell. An antimicrobial agent is bactericidal if it causes cell death. Cell death is commonly detected by the absence of cell growth in liquid growth medium (e.g., absence of turbidity) or on a solid surface (e.g., absence of colony formation on agar). Those of skill in the art know that a composition which is bacteriostatic at a given concentration may be bactericidal at a higher concentration. Certain bacteriostatic compositions are not bactericidal at any concentration.  
           [0075]    Encompassed within the definition of antimicrobial agents are compound analogs, naturally occurring, synthetic and recombinant pharmaceuticals, antibiotics, etc.  
           [0076]    As used herein, the term “antimicrobial” refers to the ability of compounds to prevent, inhibit or destroy the growth or viability of microbes such as bacteria, fungi, protozoa, and viruses. The term may also refer to the ability of compounds to prevent, reduce, or inhibit the virulence, cytotoxicity, reactogenicity, or pathogenicity of microbes such as bacteria, fungi, protozoa, and viruses.  
           [0077]    “MBC” means minimal bacteriocidal concentration defined as the lowest concentration of an antimicrobial compound that kills 99.9% of the original inoculum of a microganism, or more stringently as the lowest concentration of an antimicrobial compound that kills all of the mircroorganisms of the original inoculum.  
           [0078]    “MIC” means minimal inhibitory concentration defined as the lowest concentration of an antimicrobial agent that results in inhibition of visible growth of a microorganism (i.e., colonies on a plate or turbidity in broth culture) under standard conditions known in the art.  
           [0079]    The term “bacteria,” and “bacterial” refer to all prokaryotic organisms, including those within all of the phyla in the Kingdom Procaryotae. It is intended that the term encompass all microorganisms considered to be bacteria including Mycoplasma, Chlamydia, Actinomyces, Streptomyces, and Rickettsia. All forms of bacteria are included within this definition including cocci, bacilli, spirochetes, spheroplasts, protoplasts, etc. Also included within this term are prokaryotic organisms which are gram negative or gram positive. “Gram negative” and “gram positive” refer to staining patterns with the Gram-staining process which is well known in the art (Finegold and Martin, Diagnostic Microbiology, 6th Ed. (1982), C. V. Mosby St. Louis, pp 13-15). “Gram positive bacteria” are bacteria which retain the primary dye used in the Gram stain, causing the stained cells to appear dark blue to purple under the microscope. “Gram negative bacteria” do not retain the primary dye used in the Gram stain, but are stained by the counterstain. Thus, gram negative bacteria appear red. A bacterial organism can be one selected from the group consisting of, but not limited to,  Pseudomonas fluorescens, Pseudomonas aeruginosa, Pseudomonas acidovorans, Pseudomonas alcaligenes, Pseudomonas putida, Pseudomonas syringae, Pseudomonas aureofaciens, Pseudomonas fragi, Fusobacterium nucleatum, Treponema denticola, Porphyromonas gingivalis, Moraxella catarrhalis, Stenotrophomonas maltophilia, Burkholderia cepacia, Aeromonas hydrophilia, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Enterobacter cloacae, Enterobacter aerogenes, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Francisella tularensis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia alcalifaciens, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Acinetobacter haemolyticus, Yersinia enterocolitica, Yersinia pestis, Yersinia pseudo tuberculosis, Yersinia intermedia, Bordetella pertussis, Bordetella parapertussis, Bordetella bronchiseptica, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus haemolyticus, Haemophilus parahaemolyticus, Pasteurella multocida, Pasteurella haemolytica, Helicobacter pylori, Campylobacter fetus, Campylobacter jejuni, Campylobacter coli, Borrelia burgdorferi, Vibrio cholerae, Vibrio paramaemolyticus, Legionella pneumophila, Listeria monocytogenes, Neisseria gonorrhoeae, Neisseria meningitidis, Gardnerella vaginalis , Bacteroides spp.,  Clostridium difficile, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycrobacterium leprae, Corynebacterium diphtheriae, Corynebacterium ulcerans , Streptococcus spp., Enterococcus spp., Desulfvibrio spp., Actinomyces spp., Erwinia spp., Xanthomonas spp., Xylella spp., Clavibacter spp., Desulfomonas spp., Desulfovibrio spp., Desulfococcus spp., Desulfobacter spp., Desulfobulbus spp., Desulfosarcina spp., Deslfuromonas spp., Bacillus spp., Streptomyces spp., Clostridium spp., Rhodococcus spp., Thermatoga spp., Sphingomonas spp., Zymomonas spp., Micrococcus spp., Azotobacter spp., Norcardia spp., Brevibacterium spp., Alcaligenes spp., Microbispora spp., Micromonospora spp.,  Methylobacterium organophilum, Pseudomonas reptilivora, Pseudomonas carragienovora, Pseudomonas dentificans , Corynebacterium spp., Propionibacterium spp., Xanothomonas spp., Methylobacterium spp., Chromobacterium spp., Saccharopolyspora spp., Actinobacillus spp., Alteromonas spp., Aeronomonas spp.,  Agrobacterium tumefaciens, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus warneri, Staphylococcus cohnii, Staphylococcus saprophyticus, Staphylococcus capitis, Staphylococcus lugdunensis, Staphlyococcus intermedius, Staphylococcus hyicus, Staphylococcus saccharolyticus  and Rhizobium spp.  
           [0080]    “Fungi,” “Fungal,” “Fungus,” or “Fungal Organism” is intended to mean a eukaryotic cell having a nuclear membrane and cell wall. The subject fungi may grow as single cells (e.g., yeasts), chains (e.g., hyphae), aggregates, rafts and the like, and are not plant or mammalian cells. A fungal organism can be one selected from the group consisting of, but not limited to, Absidia spp.,  Actinomadura madurae , Actinomyces spp.,  Allescheria boydii , Altemaria spp.,  Anthopsis deltoidea , Aphanomyces spp.,  Apophysomyces eleqans , Armillaria spp.,  Arnium leoporinum , Aspergillus spp.,  Aureobasidium pullulans, Basidiobolus ranarum , Bipolaris spp.,  Blastomyces dermatitidis , Botrytis spp., Candida spp., Centrospora spp., Cephalosporium spp., Ceratocystis spp., Chaetoconidium spp., Chaetomium spp., Cladosporium spp.,  Coccidioides immitis , Colletotrichum spp, Conidiobolus spp.,  Corynebacterium tenuis , Cryptoporiopsis spp., Cylindrocladium spp., Cryptococcus spp.,  Cunninghamella bertholletiae , Curvularia spp., Dactylaria spp., Diplodia spp., Epidermophyton spp.,  Epidermophyton floccosum , Exserophilum spp., Exophiala spp., Fonsecaea spp., Fulvia spp., Fusarium spp., Geotrichum spp., Guignardia spp., Helminthosporium spp., Histoplasma spp., Lecythophora spp., Macrophomina spp., Madurella spp., Magnaporthe spp.,  Malassezia furfur , Microsporum spp., Monilinia spp., Mucor spp.,  Mycocentrospora acerina , Nectria spp., Nocardia spp., Oospora spp., Ophiobolus spp., Paecilomyces spp.,  Paracoccidioides brasiliensis , Penicillium spp.,  Phaeosclera dematioides , Phaeoannellomyces spp.,  Phialemonium obovatum , Phialophora spp., Phlyctaena spp., Phoma spp., Phomopsis spp., Phymatotrichum spp., Phytophthora spp., Pythium spp.,  Piedraia hortai, Pneumocystis carinii , Puccinia spp.,  Pythium insidiosum, Rhinocladiella aquaspersa, Rhizomucor pusillus , Rhizoctonia spp., Rhizopus spp., Saccharomyces spp.,  Saksenaea vasiformis, Sarcinomyces phaeomuriformis , Scerotium spp., Sclerotinia spp., Sphaerotheca spp.,  Sporothrix schenckii, Syncephalastrum racemosum, Taeniolella boppii , Taphrina spp., Thielaviopsis spp., Torulopsosis spp., Trichophyton spp., Trichosporon spp.,  Ulocladium chartarum , Ustilago spp., Venturia spp., Verticillium spp.,  Wangiella dermatitidis , Whetxelinia spp., Xylohypha spp., and their synonyms.  
           [0081]    By “exponential” is meant the phase of microbial growth during which the microbial population is growing at a constant and maximum rate, dividing and doubling at regular intervals (i.e., log phase growth, actively growing cells).  
           [0082]    By “glucosyltransferase activity” we mean the enzymatic activity which promotes the synthesis of complex oligosaccharides by catalyzing the addition or conformation of sugar residues, for example, the formation of cyclic-β-(1,3)-glucans.  
           [0083]    By “glucan synthesis” we mean the formation of saccharide molecules, for example cyclic-β-(1,3)-glucan, through natural or recombinant means.  
           [0084]    By “inhibitor” we mean a compound that is able to reduce the expression of a gene encoding a polypeptide and/or the expression of the polypeptide, or the biological activity of a polypeptide, e.g., a polypeptide that functions as an efflux pump or a glucosyltransferase, by at least 5%, more desirably, by at least 10%, even more desirably, by at least 25%, 50%, or 75%, and most desirably, by 90% or more.  
           [0085]    By “binding” we mean a non-covalent or covalent interaction between components. By “component” we mean a protein, a nucleic acid molecule, a glucan, or a compound. The binding components interact with a binding constant (Kd) equal to less than 1 uM, more desirably less that 100 nM, and most desirably less than 10 nM.  
           [0086]    “Transformed cell” means a cell into which (or into an ancestor of which) has been introduced, by means of recombinant DNA techniques, a DNA molecule encoding (as used herein) a polypeptide described herein (for example, an NvdB polypeptide).  
           [0087]    “Operably linked” means that a gene and a regulatory sequence(s) are connected in such a way as to permit gene expression when the appropriate molecules (e.g., transcriptional activator proteins) are bound to the regulatory sequence(s).  
           [0088]    “Transgene” means any piece of DNA which is inserted by artifice into a cell, and becomes part of the genome of the organism which develops from that cell. Such a transgene may include a gene which is partly or entirely heterologous (i.e., foreign) to the transgenic organism, or may represent a gene homologous to an endogenous gene of the organism.  
           [0089]    The term “expression vector” as used herein refers to a recombinant DNA molecule containing a desired coding sequence and appropriate nucleic acid sequences necessary for the expression of the operably linked coding sequence in a particular host organism. Nucleic acid sequences necessary for expression in prokaryotes usually include a promoter, an operator (optional), and a ribosome binding site, often along with other sequences. Eukaryotic cells are known to utilize promoters, enhancers, and termination and polyadenylation signals.  
           [0090]    “Promoter” means minimal sequence sufficient to direct transcription. Also included in the invention are those promoter elements which are sufficient to render promoter-dependent gene expression controllable for cell-type specific, tissue-specific or inducible by external signals or agents; such elements may be located in the  5 ′ or 3′ regions of the native gene.  
           [0091]    “Positioned for expression” means that the DNA molecule is positioned adjacent to a DNA sequence which directs transcription and translation of the sequence (i.e., facilitates the production of, e.g., an NdvB polypeptide, a recombinant protein or a RNA molecule).  
           [0092]    By “biofilm” is meant a population of microorganisms comprised of a single species or multiple species that form at an interface, e.g., on a biotic or abiotic surface exposed to liquid, and have increased resistance to antimicrobial agents relative to planktonic cells growing in the expotential phase. The population of cells may also have one or more of the following characteristics: a) produce or are enclosed by an extracellular matrix, b) adhere to a surface, c) form a complex architecture, d) have a gene and/or protein expression profile different from planktonic cells growing in the exponential phase under similar conditions.  
           [0093]    By “biological activity” is meant an activity associated with a microbial organism, including the formation, development, and dissolution of biofilms.  
           [0094]    By “culture system” is meant a fluid containing single-celled organisms living independently or as part of a multi-cellular community or colony. The major groups of microorganisms include archaea, bacteria, fungi, protozoa, and algae.  
           [0095]    By “expose” is meant to allow contact between a substance, including a compound, culture supernatant, or extract thereof, and a microorganism or target organism.  
           [0096]    By “environment” is meant the habitat or living conditions of a population of microorganisms, such as source microorganisms or target organisms.  
           [0097]    By “extract” is meant a product obtained from treating supernatant from a culture system to at least one purification step of any kind. In a desired embodiment, the purification is designed to isolate or increase the concentration of a biofilm modulating compound or remove undesirable elements within the supernatant.  
           [0098]    By “microorganism,” “microbial organism,” “microbe,” or “microbial” is meant a microscopic, single-celled organism that may either live independently or as part of a multi-cellular community or colony. The major groups of microorganisms include archaca, bacteria, fungi, protozoa, and algae.  
           [0099]    By “resistant” is meant a increase greater than 5% in the MBC or MIC for at least one selected antimicrobial agent, or an decreased killing under a selected growth condition in the presence of at least one antimicrobial agent compared to a control microorganism grown under the same conditions. This term may refer to the ability of a microorganism to the ability of a microorganism to maintain viability, virulence or pathogenicity in the presence of at least one antimicrobial agent compared to a control mircroorganism grown under the same conditions.  
           [0100]    By “sensitive” is meant a decrease greater than 5% in the MBC or MIC for at least one selected antimicrobial agent, or an increased killing under a selected growth condition in the presence of at least one antimicrobial agent compared to a control microorganism grown under the same conditions. This term may refer to the ability of a microorganism to the ability of a microorganism to maintain viability, virulence or pathogenicity in the presence of at least one antimicrobial agent compared to a control mircroorganism grown under the same conditions  
           [0101]    By “modulating” is meant changing, by increase, decrease or otherwise. The change may be in amount, timing, or any other parameter. A decrease or increase in, for example, cell growth, viability, virulence, or pathogenicty, may be by at least 5%, more desirably at least 10%, even more desirably at least 25%, most desirably by 50% or more.  
           [0102]    “Modulation” refers to the capacity to either enhance or inhibit a functional property of a biological activity or process (e.g., enzyme activity, receptor binding, cell growth, viability, virulence, or pathogenicty). Such enhancement or inhibition may be contingent on the occurrence of a specific event, such as activation of a signal transduction pathway, and/or may be manifest only in particular cell types.  
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0103]    [0103]FIG. 1 is a comparison of wild type and 45E7 biofilm architecture. Flow cell grown strains are shown after 3 days of growth. Both strains exhibit the typical macrocolonies and channels characteristic of these biofilms formed by  P. aeruginosa . These images are reconstructed from XZ slices through the biofilm (˜35 μm in height) using the Volocity software package.  
         [0104]    [0104]FIG. 2 presents the results of the flow cell assay for antibiotic resistance with 45E7. The left most panels (phase-contrast micrographs) show the architecture of the 24 hr old biofilm. The syto-9 panels indicate viable cells (green) and the PI (propidium iodide) panels indicate dead cells (red).  
         [0105]    [0105]FIG. 3 presents the results of the colony biofilm assay with 45E7. Colonies of the wild type (filled symbols) and the 45E7 mutant (open symbols) were transferred to solid medium without (triangles) or with 0.2 mg/ml Tb (squares). The viability of the wild-type drops ˜100-fold over 48 hrs with Tb treatment, while the 45E7 mutant drops below detection (indicated by the asterisk). In the absence of antibiotic, there is no difference in viability between the two strains.  
         [0106]    [0106]FIG. 4 demonstrates the difference between wild type and 45E7 fractionation characteristics of periplasmic glucans. The elution profiles of periplasmic extracts of the wild type (blue squares) and 45E7 mutant (red circle) on a G75 column are shown. Fractions 45-60 have anthrone positive material in periplasmic extracts from the wild type strain. This anthrone positive material is absent from the periplasmic extracts of the 45E7 mutant. Work in other organisms has shown that cyclic glucans typically elute in this size range. The Y-axis is a measure of absorbance at 620 nm.  
         [0107]    [0107]FIG. 5 presents the results of the colony biofilm assay with 30B 1. The viable cell count for the wt (filled symbols) and 30B1 mutant (open symbols) either untreated (triangles) or treated with Tb (squares) are shown over 48 hrs. There is no difference in viable counts between these strains when grown in the absence of antibiotics. The wild type decreases 100-fold in the presence of Tb, while the viable count of the 30B1 mutant is below detection at 48 hrs (indicated by the asterisk).  
         [0108]    FIGS.  6 A- 6 E presents the nucleotide (SEQ ID NO:1) and amino acid (SEQ ID NO:2) sequence of NdvB (PA1163).  
         [0109]    FIGS.  7 A- 7 K presents the nucleotide (SEQ ID NO:3) and amino acid (SEQ ID NO:4) sequence of PA1874.  
         [0110]    FIGS.  8 A- 8 B presents the nucleotide (SEQ ID NO:5) and amino acid (SEQ ID NO:6) sequence of PA1875.  
         [0111]    FIGS.  9 A- 9 D presents the nucleotide (SEQ ID NO:7) and amino acid (SEQ ID NO:8) sequence of PA1876.  
         [0112]    FIGS.  10 A- 10 B presents the nucleotide (SEQ ID NO:9) and amino acid (SEQ ID NO:10) sequence of PA1877.  
         [0113]    [0113]FIG. 11 presents the nucleotide (SEQ ID NO:11) and amino acid (SEQ ID NO:12) sequence of PA4142.  
         [0114]    [0114]FIG. 12 presents the nucleotide (SEQ ID NO:13) and amino acid (SEQ ID NO:14) sequence of PA4143.  
         [0115]    [0115]FIG. 13 presents the nucleotide (SEQ ID NO:15) and amino acid (SEQ ID NO:16) sequence of PA4144.  
         [0116]    [0116]FIG. 14 presents the nucleotide (SEQ ID NO:17) and amino acid (SEQ ID NO:18) sequence of PA2389.  
         [0117]    [0117]FIG. 15 presents the nucleotide (SEQ ID NO:19) and amino acid (SEQ ID NO:20) sequence of PA2390.  
         [0118]    [0118]FIG. 16 presents the nucleotide (SEQ ID NO:21) and amino acid (SEQ ID NO:22) sequence of PA2391.  
         [0119]    [0119]FIG. 17 presents the nucleotide sequence of a putative expression control sequence (SEQ ID NO:23) located upstream of PA1874.  
         [0120]    [0120]FIG. 18 presents the nucleotide sequence of a putative expression control sequence (SEQ ID NO:24) located upstream of PA4142.  
         [0121]    [0121]FIG. 19 presents the nucleotide sequence of a putative expression control sequence (SEQ ID NO:25) located upstream of PA2389.  
         [0122]    [0122]FIG. 20 presents the nucleotide sequence of a putative expression control sequence (SEQ ID NO:26) located upstream of PA1163.  
         [0123]    [0123]FIG. 21 presents the results the results of colony biofilm assay. The viable cell count for vector only (circles) or vector encoding PA4142-PA4144 (squares) was determined over 3 days in the presence (filled symbols) or absence (open symbols) of Tb.  
         [0124]    [0124]FIG. 22 presents the amino acid sequence (SEQ ID NO:27) of  B. japonicum  ndvB (GenBank Accession No. AAC62210).  
         [0125]    [0125]FIG. 23 presents the amino acid sequence (SEQ ID NO:28) of an  Agrobacterium tumefaciens  protein (GenBank Accession No. NP 357541).  
         [0126]    FIGS.  24 A- 24 C presents the nucleotide (SEQ ID NO:29) and amino acid SEQ ID NO:30) sequence of  Pseudomonas putida  KT2440.  
         [0127]    FIGS.  25 A- 25 C presents the nucleotide (SEQ ID NO:31) and amino acid (SEQ ID NO:32) sequence of a  Pseudomonas syringae  gene. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0128]    We posit that biofilm resistance to antimicrobial agents is part of a regulated developmental process and thus would require an identifiable set of genetic determinants. Based upon this hypothesis, a screen was designed to identify genes which, when mutated, would affect the ability of biofilm cells to resist the effects of an antimicrobial agent, while having no substantial effect on the sensitivity of planktonic cells growing in the exponential phase cells to the same antimicrobial agent. This screen was based on a modification of the microtiter plate assay that yielded surface attachment mutants (sad) of  Pseudomonas aeruginosa  and  P. fluorescens  (O&#39;Toole, G. A., and R. Kolter.  Mol. Microbiol.  30(2):295-304, 1998; O&#39;Toole, G. A., and R. Kolter,  Mol. Microbiol.  28:449-461, 1998). In the present studies, bacteria were cultured on the same minimal M63 medium expect arginine (0.4%) was used as the sole source of carbon and energy, and cultures were incubated for 24 hours. Other screens and techniques for generating mutations in cell components that function in biofilm resistance to antimicrobial agents are well known in the art, for example, the use of transposon insertion and chemical mutagenesis.  
         [0129]    The microtiter plate assay was modified to measure the increase in resistance developed by the wild type strain when growing in a biofilm. The wells of the microtiter dish are inoculated with bacteria and biofilms are allowed to form on the walls of the wells for 24 hrs in the absence of any shear force. After the biofilms had formed on the wells of the microtiter dish, the spent medium was replaced with the same media containing an antimicrobial agent. In this case, we used the aminoglycoside antibiotic tobramycin (Tb), an antibiotic that targets protein synthesis. Tb was selected because it is the primary antibiotic used to treat cystic fibrosis patients with chronic  P. aeruginosa  lung infections (Banerjee, D., and D. Stableforth,  Drugs,  60(5):1053-64, 2000; Bonsignore, C. L.,  Pediatr Nurs.  24(3):258-9, 1998; Ratjen, F,  Int J Antimicrob Agents  17(2):93-6, 2001). After exposing the biofilms to Tb for 24 hours, the antibiotic-containing medium is removed and replaced with fresh antibiotic-free medium. Any bacteria surviving in the biofilm outgrow and repopulate the planktonic phase of the wells. Viable cells were detected by plating on rich medium. Using this assay, we determined that the minimal bacteriocidal concentration (MBC) of Tb for the wt biofilm grown cells is 0.4 mg/ml. The MBC of planktonic cells was determined by adding the antibiotic to cells at the time they were inoculated into the microtiter dish, incubating the cells in the presence of antibiotic for 24 hrs, and assessing cell viability by plating on rich medium. Using this assay, the planktonic MBC was shown to be 0.008 mg/ml, a 50-fold decrease relative to the biofilm-grown bacteria.  
         [0130]    Using the assay for biofilm-related antibiotic resistance described above, a library of random  P. aeruginosa  PA14 transposon insertion mutants was screened for the inability to develop characteristic increase in resistance of biofilm-grown cells. The concentration of Tb used in the screen was 0.2 mg/ml, a concentration 25-fold greater than the planktonic MBC, but still below the concentration that will kill biofilm grown cells. From a library of 4,320 transposon mutants, forty-three putative mutants defective in biofilm-related Tb resistance were identified.  
         [0131]    The goal of the screen was to identify mutants with a biofilm-related defect in the development of antimicrobial agent resistance. Therefore, the 43 candidate mutants were subjected to a series of secondary tests to confirm the biofilm-related phenotype. Of the original 43 candidate mutants from the initial screen, two mutants grew as well as the wild type in liquid culture, formed a wild-type biofilm in the microtiter plates, and had a planktonic MBC indistinguishable from the parent strain. These mutants, designated 45E7 and 30 B1, were characterized further.  
         [0132]    Characterization of the 45E7 Mutant.  
         [0133]    In addition to the decrease in sensitivity to Tb, we determined the MBC of biofilm and planktonic cells growing in the expotential phase for gentamycin (Gm) and ciprofloxacin (Cip). Gm, like Tb, is an aminoglycoside protein synthesis inhibitor while Cip is a fluoroquinolone that targets DNA gyrase. Table 1 shows the results of these studies. For all antibiotics, there was no difference in the MBC of planktonic cells growing in the exponential phase between the wild type and 45E7 mutant. The MCB of biofilm grown 45E7 was lower for all three antibiotics when compared to the wt: Tb (16-fold), Gm (8-fold) and Cip (8-fold).  
                                                                   TABLE 1                           Bioflim and planktonic (exponential phase) resistance       of the wild type and 45E7 mutant.                Tb   Gm   Cip                Strain   MBC-P   MBC-B   MBC-P   MBC-B   MBC-P   MBC-B               Wild-type   0.008   0.4    0.04   0.5    0.004   0.05        45E7   0.008   0.025   0.04   0.06   0.004   0.006                          
 
         [0134]    One of the characteristics of biofilm grown bacteria is their distinctive architecture. Currently, it is not clear what relationship, if any, exists between the architecture of the biofilm and resistance to antimicrobial agents. Early studies of biofilm grown cells suggested that inhibition of antibiotic diffusion through the biofilm could account for the increased resistance of these communities (Costerton et al., Microbial biofilms, p. 711-745. In L. N. Omston, A. Balows, and E. P. Greenberg (ed.),  Annu. Rev. Microbiol. , vol. 49. Annual Reviews, Inc., Palo Alto, Calif., 1995). Therefore, it was possible that altering biofilm architecture could increase diffusion of Tb through the biofilm, thereby increasing sensitivity to this agent. In support of this idea, a quorum-sensing mutant of  P. aeruginosa  that exhibited altered architecture was reported to be abnormally sensitive to SDS (Davies et al.,  Science  280(5361):295-298, 1998). However, the same mutant was as resistant to killing by the antibiotic ofloxacin as the wild type biofilm cells (Brooun et al.,  Antimicrob Agents Chemother.  44(3):640-6, 2000).  
         [0135]    We utilized flow cells to analyze the architecture of the wild type and mutant strains. A flow cell allows a continuous supply of fresh medium to be delivered to a biofilm that is formed on the walls of a small, enclosed chamber. One side of this chamber is a glass cover slip, and the chamber can be mounted on to a microscope to allow for the non-destructive imaging of the biofilm. GFP-tagged wild type and 45E7 strains were inoculated into different chambers of a flow cell and the architecture of the biofilms produced by these strains was analyzed by epifluorescence microscopy. The reconstructed architecture of the wild-type and 45E7 mutant is shown in FIG. 1. This analysis showed that is no discernible difference in the architecture of these strains.  
         [0136]    Currently, there are no standard methods for determining biofilm resistance to antimicrobial agents. Thus, we utilized two other assays of biofilm antibiotic resistance to demonstrate that the phenotype observed in the microtiter plate was robust and could be observed across a number of experimental models. We chose to analyze this mutant in flow cell and colony biofilm assays.  
         [0137]    In order to document the sensitivity phenotype of the biofilms in the flow cell, the biofilm of the wild type and 45E7 strains were allowed to form. After the biofilm had developed for 24 hrs 0.2 mg/ml Tb was added to the medium. After 24 hours of exposure to Tb, flow through the cell was stopped and the BacLight viability stain was injected into the flow chambers. BacLight differentiates between cells with intact membranes (considered “live”) and those with damaged membranes (considered “dead”). After 15 minutes of staining, flow through the chamber was resumed and following a 15 minute wash the cells were examined by epifluorescent microscopy (FIG. 2). The left-hand panels show phase contrast images—there was no difference in biofilm architecture between these strains (see also FIG. 1). The center and right panel shows that there were more live than dead cells in the Tb-treated biofilm of the wild type strain. Conversely, there were more dead cells than live ones in the Tb-treated biofilm of the 45E7 mutant strain. This result confirmed the drug sensitivity phenotype first observed in the microtiter plate assay.  
         [0138]    We also used the quantitative colony biofilm assay to document the 45E7 mutant phenotype. It has been reported that bacterial colonies develop some of the properties associated with biofilms, including increased resistance to biocides (Anderl et al.,  Antimicrob Agents Chemother.  44(7):1818-24, 2000; Stewart, P. S.,  Biotechnol Bioeng.  59(3):261-72, 1998). Colony biofilms were formed on polycarbonate filters for 48 hrs then transferred to solid media containing Tb. Viable cell numbers in the colony was determined after 4, 24 and 48 hours of exposure to Tb (FIG. 3). The 45E7 biofilm cells remained as resistant to the effects of Tb as the wild type at the first two time points assayed. However, at 48 hours, while the wild type biofilm cell viability was only reduced by 100-fold, no viable cells were detected for the 45E7 mutant. In the absence of Tb, there was difference in viability between the two strains tested. Taken together with the data presented above, we concluded that the 45E7 mutant is less resistant to the antimicrobial effects of Tb when growing in a biofilm.  
         [0139]    The 45E7 Mutation is in PA1163, a Putative Glucosyltransferase  
         [0140]    The transposon insertion carried by the 45E7 strain was cloned and the DNA flanking the transposon sequenced and compared to the published sequence of  P. aeruginosa  PAO1. The gene disrupted in 45E7, PA1163 (GenBank Accession No. ______) is 58% identical to a  Bradyrhizobium japonicum  gene ndvB. The ndvB gene of  Bradyrhizobium japonicum  codes for a glucosyltransferase that is required for the synthesis of cyclic-b-(1,3), b-(1,6)-glucans (Bhagwat et al.,  J Bacteriol.  178(15):4635-42, 1996). Located in the periplasm and extracellular media, cyclic glucans have been shown to play a role in growth in low osmotic media and in plant infection (Breedveld, M. W., and K. J. Miller,  Microbiol Rev.  58(2):145-61, 1994). In  B. japonicum , another gene, ndvC acts in concert with ndvB to form the b-(1,3), b-(1,6) linkages. ndvC mutants produce glucans with only b-(1,3) linkages (Bhagwat et al.,  Plant Physiol.  119(3):1057-64, 1999). Furthermore, in  Sinorhizobium meliloti , the ndvA gene product is thought to be required for the export of cyclic glucans from the periplasm to the extracellular medium (Breedveld, M. W., and K. J. Miller.  Microbiol Rev.  58(2):145-61, 1994). Upon investigation of the  P. aeruginosa  genome, we noticed that there is no ndvC homolog present, but there are three genes with ˜50% homology to  S. meliloti  ndvA. Thus, it seemed likely that  P. aeruginosa  produces periplasmic and extracellular b-(1,3)-glucans. To confirm that cyclic glucans were made by the wild type strain and that these glucans were altered or not present in the ndvB PA1163 mutant we characterized the periplasmic and extracellular polysaccharides produced by these strains. Ethanol extracts from both the periplasm and the extracellular medium of these strains were fractionated by gel filtration chromatography to estimate the molecular weight of the material (Wang et al.,  J Bacteriol.  181(15):4576-83, 1999). Fractions were assayed for polysaccharides using the colorometric anthrone-sulfuric acid method. The anthrone assay measures the total concentration of carbohydrate, or monosaccharide equivalents, in a sample (Loewus, F. A.,  Anal. Chem.  24:219, 1952). Anthrone-positive extracellular material from the wild type eluted from the sizing column in fractions that corresponded to a molecular weight (MW) of approximately 1500, while the mutant produced no anthrone positive fractions in the 1500MW range. In contrast, anthrone-positive material from the 45E7 mutant extracts eluted in the column void volume, indicates a MW of greater than 80,000, possibly indicating an aggregate of polysaccharides.  
         [0141]    The material extracted from the periplasm was also fractionated by gel filtration chromatography and it was found that the anthrone-positive material produced by the wild type and mutant strains also differed (FIG. 4). While the wild type strain produced material that eluted across the molecular weight range of the column, the mutant strain lacked anthrone-positive material in fractions where cyclic glucans typically elute (Wang et al.,  J Bacteriol.  181(15): 4576-83, 1999).  
         [0142]    Based on the current understanding of the roles of cyclic glucans in  B. japonicum, S. meliloti  and  Agrobacterium tumefaciens , we envisioned three possible models to describe the role of these molecules in the development of resistance in biofilm populations. Cyclic glucans may be required to: i) maintain the osmotic balance within biofilms, ii) sequester antimicrobial agents in biofilm-grown cells, or iii) act as signaling molecules required for the development of resistance to antimicrobial agents.  
         [0143]    To test the hypothesis that cyclic glucans are important for hypo-osmotic adaptation, we examined the wild type and -PA1163 strains for their ability to survive and grow in low osmotic strength medium. As a first step, we diluted overnight cultures into water and monitored the survival of the wild type and mutant strains over 24 hrs. There was no difference in the survival of these strains in water. We assessed the growth of both strains in liquid {fraction (1/10)} strength minimal salts M63 medium (a hypo-osmotic medium compared to full strength M63) and on solid GYM media with no salt. The ndvB mutant of  S. meliloti  grows very slowly on GYM media, while the wild type shows no growth defect (Bhagwat et al.,  FEMS Microbiol Lett.  114(2): 139-44, 1993; Cangelosi et al.,  J Bacteriol.  172(4):2172-4, 1990; lelpi et al.,  J Biol Chem.  265(5):2843-51, 1990). There was no difference in the growth of the wild type and PA1163 mutant of  P. aeruginosa  on these media, suggesting that PA1163 may not be involved in hypo-osmotic adaptation in  P. aeruginosa.    
         [0144]    A number of reports suggest that cyclic glucans can bind or sequester a range of chemically unrelated compounds [reviewed in (Breedveld, M. W., and K. J. Miller.  Microbiol Rev.  58(2):145-61, 1994)]. This suggested the possibility that glucans in the extracellular and/or periplasmic space might sequester antimicrobial agents and thus prevent them from entering into the cytoplasm of the bacterial cell. To test this idea, we utilized the putative cyclic glucan fractions isolated by gel filtration chromatography from the periplasm of the wild-type strain (see above). This material was incubated in the presence of Tb, then spotted on a filter disk placed on a freshly spread lawn of  E. coli . Filter disks spotted with Tb alone, glucans alone, and water were also included as controls. Preliminary studies with the disk-diffusion assay indicated that glucan-treated Tb was decreased in its zone of killing as compared to Tb alone. Glucans had no antimicrobial activity at the concentrations used in these assays. These data indicate that the presence of cyclic glucans can decrease the antimicrobial activity of Tb, and is consistent with a role for glucans in the sequestering of antimicrobial agents.  
         [0145]    PA1163 mRNA is Expressed in Biofilm Grown Cells, but not in Planktonic Cells  
         [0146]    In order to investigate the expression pattern of PA1163 we used a continuous flow system to grow planktonic and biofilm bacteria. Total mRNA was harvested from both biofilm and planktonic cells and RT-PCR used to detect the presence of PA1163 transcript. In this study expression of rplU, a gene known to be expressed in both planktonic cells and biofilm grown cells, was used as a control. Chromosomal DNA was used to identify the expected size of the PA1163 mRNA. This study revealed that PA1163mRNA is expressed in biofilm grown cells and is undetectable in planktonic cells. These data indicate that PA1163 may be poorly expressed (or not expressed at all) under planktonic conditions. The fact that PA1163 appears to be expressed only in biofilm-grown cells is consistent with our model that PA1163 plays a role in biofilm-related antibiotic resistance.  
         [0147]    [0147] P. aeruginosa  PA1163 can Complement a ndvB  S. meliloti  Mutant  
         [0148]    The Rm8519 ndvB mutant of  S. meliloti  exhibits a hypo-osmotic growth phenotype. In order to investigate whether  P. aeruginosa  PA1163 can complement this mutant, and is thus likely to encode a glucosyltransferase, we introduced a vector pSMC654 containing the  P. aeruginosa  PA1163 gene into the ndvB mutant of  S. meliloti . As a control, wild type strain and the ndvB mutant of  S. meliloti  were transformed with empty vector pSW213 alone. The PA1163 containing vector (but not the empty vector) complemented the ndvB mutant of  S. meliloti  for its hypo-osmotic growth phenotype. Therefore, the PA 1163 gene of  P. aeruginosa  can functionally substitute for  S. meliloti  ndvB, strongly suggesting that  P. aeruginosa  PA1163 protein is a glucosyltransferase.  
         [0149]    Wild-Type  P. aeruginosa , but not PA1163 Mutants Produce Glucans.  
         [0150]    We compared carbohydrates produced by wild-type  P. aeruginosa  to purified cyclic glucan from  S. meliloti  using chromatographic analysis. This analysis revealed that glucans produced by wild-type  P. aeruginosa  elute in same fractions as purified cyclic glucan from  S. meliloti . Similarly eluting material was not detectable in carbohydrates produced by a  P. aeruginosa  PA1163 mutant. Moreover, analysis of the pooled glucan-containing fractions from the wild-type  P. aeruginosa  strain showed that glucose is the predominate sugar as judged by a glucose standard and consistent with their identification as glucans. The same fractions from the PA1163 mutant did not contain glucose.  
         [0151]    Glucans Interact with Tb in vitro  
         [0152]    If periplasmic glucans were indeed sequestering Tb, we predicted that these molecules should interact in vitro. To test this possibility, we examined in vitro interactions of purified glucans with Tb. Tb was loaded onto a C18 column and its elution profile was monitored by a bioassay on a lawn of sensitive bacteria. A zone of clearing indicated the presence of Tb in a fraction. Tb was detected in the column flow-through and first water wash, but not in any subsequent fractions. In contrast, when a crude periplasmic carbohydrate extracted from the wild type strain was pre-loaded onto the column, a portion of the Tb was retained on the column and eluted with 25% acetonitrile. Thus, the presence of the wild type extract on the column retarded the elution of Tb, suggesting that periplasmic glucans interacted with Tb.  
         [0153]    To determine which components of the crude extract were responsible for the Tb retention on the C18 column, we performed the same experiment as above except the C-18 column was pre-loaded with partially pure glucan-containing fractions from a G-75 gel filtration sizing column. Tb was retained on the column pre-loaded with material from the wild type extract and eluted from the column with 25% acetonitrile. In contrast, no Tb activity was present in the 25% acetonitrile fraction from the column preloaded with the corresponding fractions isolated from the  P. aeruginosa  PA1163 mutant. Only the material present in glucan-containing fractions derived from the wild type interacted with and changed the chromatographic behavior of Tb.  
         [0154]    Characterization of the 30B1 Mutant.  
         [0155]    A second mutant strain defective in biofilm specific Tb resistance, designated 30B1, was isolated and characterized. Like 45E7, this strain grew as well as the wild type in liquid culture, formed a wild-type biofilm in the microtiter plates, and had an exponential phase planktonic MBC indistinguishable from the parent strain. This mutant is also less resistant to the antibiotics Gm and Cip. In all cases, the decrease in resistance of this mutant is less than the decrease observed for the 45E7 mutant. These results suggest that the functions disrupted in this strain debilitate biofilm-related antibiotic resistance via a different mechanism.  
                                                                   TABLE 2                           Bioflim and planktonic resistance of the wild type and 45E7 mutant.                Tb   Gm   Cip                Strain   MBC-P   MBC-B   MBC-P   MBC-B   MBC-P   MBC-B               Wild-type   0.008   0.4   0.04   0.5    0.004   0.05        30B1   0.008   0.1   0.04   0.25   0.004   0.0125                          
 
         [0156]    We also examined the architecture of this mutant and showed that it was identical to the wild-type strain as judged by the flow cell assay and analysis of the biofilms by fluorescence microscopy (data not shown).  
         [0157]    The colony biofilm assay was also utilized to assess the antibiotic resistance of the 30B1 mutant strain as described above. As was observed for the 45E7 mutant, the 30B1 strain showed a marked decrease in resistance to Tb as compared to the wild-type strain (FIG. 5). After 48 hrs of exposure to Tb, the viability of the wild type had dropped ˜100-fold, while there were no viable cells detected for the 30B1 mutant (a drop in viable count of ˜10 9 ). This experiment confirms the results obtained in the microtiter dish assay.  
         [0158]    The 30B1 Mutation is in PA1874  
         [0159]    The transposon insertion carried by the 30B1 strain was cloned and the DNA flanking the transposon was sequenced and compared to the published sequence of  P. aeruginosa  PAO1. The open reading frame (ORF) disrupted by the transposon, PA1874, encodes a predicted outer membrane protein with sequence similarity to LapA of  P. putida  (42% similarity) and Bap of  Staphylococcus aureus  (46% similarity). Both of these proteins are important for biofilm development. LapA is required for the colonization of seeds by  P. putida  and Bap was identified in a screen for mutants unable to make a biofilm (Cucarella et al.,  J Bacteriol.  183(9):2888-2896, 2001; Espinosa-Urgel et al.,  J Bacteriol.  182(9):2363-2369, 2000).  
         [0160]    In  P. aeruginosa , PA1874 is the first gene in a predicted four gene operon that, in addition to PA1874, includes: PA1875, an OprN-like outer membrane protein that bears some similarity to outer membrane proteins in the RND family; PA1876, a protein that is similar to an ABC family ATPase; and PA1877, a protein that appears to be a ABC family membrane fusion protein.  
         [0161]    As noted above, PA1875 is similar to OprN. The OprN protein is part of the MexEF-OprN multidrug efflux pump, a RND-type efflux pump which is involved in fluoroquinolone resistance (Nikaido, H. 1994. Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science. 264(5157):382-8; Piddock, L. J. 1999. Mechanisms of fluoroquinolone resistance: an update 1994-1998. Drugs. 58(Suppl 2):11-8. Thus, the PA1874-PA1877 operon encodes components of both multi-drug efflux pumps and ABC transporters. Although other RND efflux pumps include an outer membrane protein and a membrane fusion protein, they do not typically include a ABC family cytoplasmic membrane-located ATPase and they do not typically require two outer membrane proteins (Poole, K., J Mol Microbiol Biotechnol. 3(2):255-64, 2001). Thus, the PA1874-PA1877 operon appears to encode anew type of hybrid efflux pump that combines features of a RND multidrug efflux pumps and ABC transporters.  
         [0162]    Identification of Additional Hybrid Efflux Pumps  
         [0163]    We analyzed the sequence of the  P. aeruginosa  genome in a effort to identify other genetic loci that resemble PA1874-PA1877. We identified two other genetic loci, PA4142-PA4143 and PA2389-PA2391, that are similar to the PA1874-PA1877 operon in both sequence and organization. Each of these loci appears to encode three, rather than four polypeptides. These loci encode putative hybrid efflux pumps that are predicted to play a role in biofilm resistance.  
         [0164]    Table 3 summarizes information for each of the proteins in the three identified hybrid efflux pump operons. Putative expression control sequences upstream of PA1874,PA4142, and 2389 are shown in FIGS. 17, 18 and  19  respectively.  
                                     TABLE 3                           Summary of Hybrid Efflux Pump Genes                    Nucleotide                   Proposed   and Protein   Nucleic Acid   Protein SEQ       Name   Function   Sequence   SEQ ID NO.   ID NO.               PA1874   OMP       SEQ ID NO:3   SEQ ID NO:4       PA1875   OprN-like       SEQ ID NO:5   SEQ ID NO:6           OMP (similar           to RND family           OMP)       PA1876   ABC family       SEQ ID NO:7   SEQ ID NO:8           ATPase       PA1877   MFP       SEQ ID NO:9   SEQ ID NO:10       PA4142   MFP       SEQ ID NO:11   SEQ ID NO:12       PA4143   ABC family       SEQ ID NO:13   SEQ ID NO:14           ATPase       PA4144   OprM-like       SEQ ID NO:15   SEQ ID NO:16           OMP efflux           pump protein           (similar to           RND family           OMP)       PA2389   MFP       SEQ ID NO:17   SEQ ID NO:18       PA2390   ABC family       SEQ ID NO:19   SEQ ID NO:20           ATPase       PA2391           SEQ ID NO:21   SEQ ID NO:22                  
 
         [0165]    The putative Hybrid Efflux Pump Encoded by PA4144-PA4146 Appears to Play a Role in Biofilm Resistance  
         [0166]    In order to determine whether the putative hybrid efflux pump encoded by PA4144-PA4146) plays a role antibiotic resistance, we inserted a nucleotide sequence that includes PA4144-PA4146 into a medium copy plasmid pSMC32 and used the resulting vector pSMC51 to transform  P. aeruginosa  strain PA14. Neither the PA4144-PA4146 encoding vector nor the parent plasmid had any effect on the resistance of planktonic  P. aeruginosa  to Tb.  
         [0167]    We also investigated the resistance of the transformed cells to Tb when grown as a biofilm. Interestingly, wild-type  P. aeruginosa  carrying the PA4144-PA4146 encoding vector became hypersensitive to antibiotics in the colony biofilm assay for reasons that are not clear, but may be due to the increased metabolic burden of carrying a plasmid (see FIG. 21). Therefore, we created a “synthetic sensitivity” to antibiotics by having the wild type  P. aeruginosa  strain carry a parent plasmid (no PA4144-PA4146 encoding sequences). As shown in FIG. 21, a  P. aeruginosa  strain carrying both this parent plasmid and the PA4144-PA4146 encoding vector regained a level of antibiotic resistance similar to the of an untransformed strain (no parent plasmid and no PA4144-PA4146 encoding vector). These indirect data suggest that the hybrid efflux pump encoded by PA4144-PA4146 has the ability to confer antibiotic resistance in biofilm-grown bacteria and supports our hypothesis that these novel, hybrid efflux pumps play a role in biofilm-related antibiotic resistance.  
         [0168]    Identification of Additional Proteins Resembling PA1163  
         [0169]    We used sequence homology searching to identify genes encoding proteins that are likely homologs. The proteins encoded by these genes, like ndvB, are expected to play a role in biofilm resistance. The genes are:  B. japonicum  ndvB (GenBank Accession No. AAC62210; FIG. 22; SEQ ID NO:27);  Agrobacterium tumefaciens  unannotated sequence (GenBank Accession No. NP 357541; FIG. 23; SEQ ID NO:28);  Pseudomonas putida  KT2440 (FIGS.  24 A- 24 C; SEQ ID Nos:29 and 30); and a  Pseudomonas syringae  gene (FIGS.  25 A- 25 C; SEQ ID Nos:31 and 32).  
         [0170]    Uses of the Identified Genes  
         [0171]    The data described herein suggest two novel mechanisms for biofilm-related antimicrobial resistance. We have shown that a mutant unable to acquire biofilm-related resistance to the antibiotic Tb is defective in glucan synthesis. The  P. aeruginosa  ndvB mutant had increased biofilm-related sensitivity to Gm and Cip. We propose that these glucans sequester Tb and thereby prevent access of this antibiotic to the cytoplasm of the bacteria. This observation is consistent with previous reports that glucans can bind a range of chemically distinct molecules (Breedveld, M. W., and K. J. Miller.  Microbiol Rev.  58(2):145-61, 1994). The ability to bind a range of biocides is also consistent with the reported ability of biofilms to develop broad resistance to antimicrobial agents [reviewed in (Mah, T.-F., and G. A. O&#39;Toole.  TIMS  9:34-39,2001)].  
         [0172]    Based on our data, we submit that compounds that modulate the expression of ndvB or the function of an NdvB polypeptide, such that there is a decrease in ndvB gene transcription, ndvB mRNA translation, or NdvB polypeptide function, are expected to promote a decrease in microbial resistance to antimicrobial agents, possibly due to the loss of, or lower levels of, glucan synthesis. Compounds which alter the activity of PA1163 can be identified using an assay for ndvB activity, e.g., the assay described by Bhagwat et al. ( J. Bact.  178:4635-42, 1994). Compounds that modulate function of the identified homologs of ndvB are also expected to promote a decrease in microbial resistance to antimicrobial agents, possibly due to the loss of, or lower levels of, glucan synthesis. This decrease in resistance is predicted to occur in biofilms, but may also occur in other physiological states as well as in cells having genetic changes leading to increased resistance.  
         [0173]    We have also identified a novel efflux pump that is required for full biofilm-related antibiotic resistance. This pump appears to be a hybrid between known efflux pumps of the RND superfamily and ABC transporters. Efflux pumps typically have broad substrate specificity, which is consistent with the decrease in resistance of the 30B1 mutant to Tb, Gm and Cip.  
         [0174]    Compounds that decrease either the expression of PA1874 or one or more of the following: PA1875, PA1876, and PA1877, or the function of the corresponding polypeptides, such that there is a decrease in gene transcription, mRNA translation, or polypeptide function of one or more of PA1874, PA1875, PA1876, or PA1877 are expected to promote a decrease in microbial resistance to antimicrobial agents. Similarly, compounds that decrease either the expression of any of PA4142-PA4144 and PA2389-PA2391, or the function of the corresponding polypeptides, such that there is a decrease in gene transcription, mRNA translation, or polypeptide function of one or more of PA4142-PA4144 and PA2389-PA2391 are expected to promote a decrease in microbial resistance to antimicrobial agents. This decrease in resistance is predicted to occur in biofilms, but may also occur in other physiological states as well as in cells having genetic changes leading to increased resistance.  
         [0175]    Compounds which alter the expression of one or more of the hybrid efflux pump genes described herein can be identified using a reporter construct in which a reporter gene is operably linked to an expression control region located upstream of PA1873, PA4142 or PA2389 (see Table 3). The reporter construct is introduced into a cell, e.g., bacterial cell such as a  P. aeruginosa  cell. The cell is exposed to a test compound and the expression of the reporter gene is monitored.  
         [0176]    One method to further examine the function of the novel efflux pumps is to express the components of the efflux pump in a variety of cell types, prokaryotic and eukaryotic, and use it to screen for compounds which overcome (inhibit) the action of the efflux pump. Bacteria have developed several different mechanisms to overcome the action of antibiotics. These mechanisms of resistance can be specific for a molecule or a family of antibiotics, or can be non-specific and be involved in resistance to unrelated antibiotics. Several mechanisms of resistance can exist in a single bacterial strain, and those mechanisms may act independently or they may act synergistically to overcome the action of an antibiotic or a combination of antibiotics. Specific mechanisms include degradation of the drug, inactivation of the drug by enzymatic modification, and alteration of the drug target (B. G. Spratt, Science 264:388 (1994)). There are, however, more general mechanisms of drug resistance, in which access of the antibiotic to the target is prevented or reduced by decreasing the transport of the antibiotic into the cell or by increasing the efflux of the drug from the cell to the outside medium. Both mechanisms can lower the concentration of drug at the target site and allow bacterial survival in the presence of one or more antibiotics which would otherwise inhibit or kill the bacterial cells. Some bacteria utilize both mechanisms, combining a low permeability of the cell wall (including membranes) with an active efflux of antibiotics. (H. Nikaido, Science 264:382-388 (1994)).  
         [0177]    Different pumps can efflux specifically a drug or group of drugs, such as the NorA system that transports quinolones, or Tet A that transports tetracyclines, or they can efflux a large variety of molecules, such as certain efflux pumps of  P. aeruginosa . In general, efflux pumps have a cytoplasmic component and energy is required to transport molecules out of the cell. Some efflux pumps have a second cytoplasmic membrane protein that extends into the periplasm. At least some efflux pumps of  P. aeruginosa  have a third protein located in the outer membrane.  
         [0178]    Efflux pumps are involved in antibiotic resistance since, in some cases, they can remove a significant fraction of the antibiotic molecules which manage to enter the cells, thereby maintaining a very low intracellular antibiotic concentration. To illustrate,  P. aeruginosa  laboratory-derived mutant strain 799/61 which does not produce any measurable amounts of efflux pump is 8 to 10 fold more susceptible to tetracycline and ciprofloxacin than the parent strain  P. aeruginosa  799, which synthesizes efflux pumps. Also, null mutants of mexA, the cytoplasmic component of a  P. aeruginosa  efflux pump, are more susceptible to antibiotics than the wild type.  
         [0179]    The physiological role of efflux pumps has not been clearly defined yet. They are involved in drug resistance but they also are involved in the normal physiology of the bacterial cell. The efflux pump coded in the mexA operon of  P. aeruginosa  has been shown to be regulated by the iron content of the medium, and it is co-regulated with the synthesis of the receptors of siderophores. Siderophores are molecules that are needed for bacterial growth under iron starvation conditions, such as during infection of an animal. They are synthesized in the cytoplasm and exported when the bacterial cell needs iron. Siderophores scavenge iron within the infected animal and return the iron to the microbe to be used for essential microbial processes. Since there is essentially no free iron in the bodies of animals, including the human body, the production of siderophores by infecting bacteria is an important virulence factor for the progress of the infection.  
         [0180]    One aspect of this invention concerns the identification of compounds that are inhibitors of a hybrid efflux pump described herein. Such efflux pumps export substrate molecules from the cytoplasm in an energy-dependent manner, and the exported substrate molecules can include antibacterial agents or other antimicrobial agents. Such efflux pump inhibitors are useful, for example, for treating microbial infections by reducing the export of a co-administered antimicrobial agent or by preventing the export of a compound synthesized by microbes (e.g., bacteria) to allow or improve their growth. An example of reducing the export of such a compound is inhibiting iron availability for the microbe by reducing the export of siderophores. Thus, this invention provides methods to identify compounds that are efflux pump inhibitors.  
         [0181]    One recent hypothesis to explain biofilm-related antibiotic resistance invoked the development of “persistors”, or a subset of bacteria that develop high level resistance to antimicrobial agents. As is the case for the development of biofilm architecture we propose that entry into this persistent state requires a specific set of genes and their gene products. The isolation of mutants defective in biofilm-related resistance, such as PA1163, supports the hypothesis that there is a distinct genetic basis for this biofilm-related resistance and our approach has begun to identify these components.  
         [0182]    The resistance of biofilms to traditional antibiotic therapy in the clinical setting is an ongoing problem. Our invention, however, provides new strategies to block the development of this resistance by identifying the genes and gene products responsible for resistance. In addition to providing a means for inhibiting biofilms, we provide a co-therapeutic approach where traditional antibiotics are combined with a drug that interferes with biofilm-related resistance to render biofilms, and possibly related physiological states, more susceptible to treatment.  
     
       
       
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            1 

atg tct tca cgc aag atc ggg ctc aac ctg gtg gtc atc gtc gcc ctg       48 
Met Ser Ser Arg Lys Ile Gly Leu Asn Leu Val Val Ile Val Ala Leu 
 1               5                   10                  15 

gcc gcc ctc ttc acc ggc atc tgg gcc ctg tac aac cgt ccg gtc agc       96 
Ala Ala Leu Phe Thr Gly Ile Trp Ala Leu Tyr Asn Arg Pro Val Ser 
             20                  25                  30 

gta ccg gac tgg ccg gaa cgc atc tcc ggc ttc tcc ttc tcg ccg ttc      144 
Val Pro Asp Trp Pro Glu Arg Ile Ser Gly Phe Ser Phe Ser Pro Phe 
         35                  40                  45 

cgc ctc aac cag aac ccg cag agc ggc cgc tac ccc agc gcc gaa cag      192 
Arg Leu Asn Gln Asn Pro Gln Ser Gly Arg Tyr Pro Ser Ala Glu Gln 
     50                  55                  60 

atg cgc acc gac ctg gaa ctg gtc gcc cgg cac acc cac agc atc cgc      240 
Met Arg Thr Asp Leu Glu Leu Val Ala Arg His Thr His Ser Ile Arg 
 65                  70                  75                  80 

acc tat tcg gtc cag ggc gcg ctc ggc gac atc ccg gcg ctg gcc gag      288 
Thr Tyr Ser Val Gln Gly Ala Leu Gly Asp Ile Pro Ala Leu Ala Glu 
                 85                  90                  95 

gcg ttc ggc ctg cgc gtc agc ctg ggc atc tgg ctc ggc ccg gac ctg      336 
Ala Phe Gly Leu Arg Val Ser Leu Gly Ile Trp Leu Gly Pro Asp Leu 
            100                 105                 110 

gcc agc aac gag gcc gag atc gcc cgc gcc atc cgc atc gcc aac gag      384 
Ala Ser Asn Glu Ala Glu Ile Ala Arg Ala Ile Arg Ile Ala Asn Glu 
        115                 120                 125 

tcg ccg agc gtg gtg cga gtg ata gtc ggc aac gag gcg ctg ttc cgc      432 
Ser Pro Ser Val Val Arg Val Ile Val Gly Asn Glu Ala Leu Phe Arg 
    130                 135                 140 

cgc gag gtg acg gcg gaa cag ttg atc gcc tac ctc gac cgg gtc cgc      480 
Arg Glu Val Thr Ala Glu Gln Leu Ile Ala Tyr Leu Asp Arg Val Arg 
145                 150                 155                 160 

gcg gcg gtc aag gtt ccg gtg acc acc gcc gaa cag tgg cac gtc tac      528 
Ala Ala Val Lys Val Pro Val Thr Thr Ala Glu Gln Trp His Val Tyr 
                165                 170                 175 

cgc gaa cac ccg gaa ctg gcg caa cac gtc gac ctg atc gcc gcc cac      576 
Arg Glu His Pro Glu Leu Ala Gln His Val Asp Leu Ile Ala Ala His 
            180                 185                 190 

gtc ctg ccc tac tgg gag gcc acg ccg gtg gcc gac gcg gtg gac ttc      624 
Val Leu Pro Tyr Trp Glu Ala Thr Pro Val Ala Asp Ala Val Asp Phe 
        195                 200                 205 

gtg ctc gaa cgc gcg cgc gaa ctc aag gcc gcc ttc ccg agg aag ccg      672 
Val Leu Glu Arg Ala Arg Glu Leu Lys Ala Ala Phe Pro Arg Lys Pro 
    210                 215                 220 

ctg ctg ctc gcc gag gtc ggc tgg ccg agc aac ggg cgc atg cgc ggc      720 
Leu Leu Leu Ala Glu Val Gly Trp Pro Ser Asn Gly Arg Met Arg Gly 
225                 230                 235                 240 

agc gcc gag gcg aca ccc gcg gac cag gcc atc tac ctg cgg cgc ctg      768 
Ser Ala Glu Ala Thr Pro Ala Asp Gln Ala Ile Tyr Leu Arg Arg Leu 
                245                 250                 255 

acc aac gcg ctc aac ggc gaa ggc tac agc tac ttc gtc atc gaa gcc      816 
Thr Asn Ala Leu Asn Gly Glu Gly Tyr Ser Tyr Phe Val Ile Glu Ala 
            260                 265                 270 

ttc gac cag ccc tgg aag gtc agc gcc gaa ggc tcg gtg ggc gcc tac      864 
Phe Asp Gln Pro Trp Lys Val Ser Ala Glu Gly Ser Val Gly Ala Tyr 
        275                 280                 285 

tgg ggc gtc tac aac gcc gac cgc aag gcc aag ttc aac ttc acc ggg      912 
Trp Gly Val Tyr Asn Ala Asp Arg Lys Ala Lys Phe Asn Phe Thr Gly 
    290                 295                 300 

ccg gtg gtg ccg att ccc aag tgg cgc gcc ctg gcc atc gcc tcg gcg      960 
Pro Val Val Pro Ile Pro Lys Trp Arg Ala Leu Ala Ile Ala Ser Ala 
305                 310                 315                 320 

gta ctc gcg gta ctc gcc ttc acc ctg ctg ctg atc gac agt tcc tcg     1008 
Val Leu Ala Val Leu Ala Phe Thr Leu Leu Leu Ile Asp Ser Ser Ser 
                325                 330                 335 

ctg cgc cag cgc ggg agg acc ttc ctc gcc gtg gtc tcg ttc gcc tgc     1056 
Leu Arg Gln Arg Gly Arg Thr Phe Leu Ala Val Val Ser Phe Ala Cys 
            340                 345                 350 

gcc tcg gtg ctg gtg tgg atc gcc tac gac tac agc cag cag tac agc     1104 
Ala Ser Val Leu Val Trp Ile Ala Tyr Asp Tyr Ser Gln Gln Tyr Ser 
        355                 360                 365 

acc tgg ttc agc ctg acc gtc ggc gcg ttg ctg ggc gtc ggc gcg cta     1152 
Thr Trp Phe Ser Leu Thr Val Gly Ala Leu Leu Gly Val Gly Ala Leu 
    370                 375                 380 

ggg gtg gtc atc gtg ctg ttc acc gag gcc cac gag ctg gcc gag gcg     1200 
Gly Val Val Ile Val Leu Phe Thr Glu Ala His Glu Leu Ala Glu Ala 
385                 390                 395                 400 

gtc tgg acg cgc aag cgg cgc cgg cca ttc ctg ccg atc acc gcc gcg     1248 
Val Trp Thr Arg Lys Arg Arg Arg Pro Phe Leu Pro Ile Thr Ala Ala 
                405                 410                 415 

cgg gcc tat cgg ccc aag gtg tcg atc cac gtg ccc tgc tac aac gag     1296 
Arg Ala Tyr Arg Pro Lys Val Ser Ile His Val Pro Cys Tyr Asn Glu 
            420                 425                 430 

ccg ccg gaa ctg ctg aag cag acc ctc gac gcc ctt gcc cgc ctc gac     1344 
Pro Pro Glu Leu Leu Lys Gln Thr Leu Asp Ala Leu Ala Arg Leu Asp 
        435                 440                 445 

tac ccg gac tac gaa gtc ctg gtg atc gac aac aac acc cgc gac ccg     1392 
Tyr Pro Asp Tyr Glu Val Leu Val Ile Asp Asn Asn Thr Arg Asp Pro 
    450                 455                 460 

gcc gtc tgg cag ccg gtc gag gcg cac tgc gcg cgc ctg ggc gag cgc     1440 
Ala Val Trp Gln Pro Val Glu Ala His Cys Ala Arg Leu Gly Glu Arg 
465                 470                 475                 480 

ttc cgc ttc ttc cac gtt gcc ccg ctg gaa ggc ttc aag gcc ggc gcg     1488 
Phe Arg Phe Phe His Val Ala Pro Leu Glu Gly Phe Lys Ala Gly Ala 
                485                 490                 495 

ctg aac ttc gcc ctg ggc cac gtg gcg gcg gac gtc gag gtg gtc gcg     1536 
Leu Asn Phe Ala Leu Gly His Val Ala Ala Asp Val Glu Val Val Ala 
            500                 505                 510 

gtg atc gac gcc gac tac tgc gtc gac ccc gac tgg ctc agg cac atg     1584 
Val Ile Asp Ala Asp Tyr Cys Val Asp Pro Asp Trp Leu Arg His Met 
        515                 520                 525 

gtg ccg cac ttc ggc gac ccg cgg atc gcc gtg gtg cag tcg ccg cag     1632 
Val Pro His Phe Gly Asp Pro Arg Ile Ala Val Val Gln Ser Pro Gln 
    530                 535                 540 

gac tac cgc gac cag cac gag agc gcc ttc aag cgg ctc tgc tac gcc     1680 
Asp Tyr Arg Asp Gln His Glu Ser Ala Phe Lys Arg Leu Cys Tyr Ala 
545                 550                 555                 560 

gag tac aag ggc ttc ttc cac atc ggc atg gtc acc cgc aac gac cgc     1728 
Glu Tyr Lys Gly Phe Phe His Ile Gly Met Val Thr Arg Asn Asp Arg 
                565                 570                 575 

gac gcg atc atc gag cac ggc acc atg acc atg atc cgg cgc agc gtg     1776 
Asp Ala Ile Ile Glu His Gly Thr Met Thr Met Ile Arg Arg Ser Val 
            580                 585                 590 

ctg gac gag ctg aga tgg ccg gaa tgg tgc atc acc gag gac gcc gag     1824 
Leu Asp Glu Leu Arg Trp Pro Glu Trp Cys Ile Thr Glu Asp Ala Glu 
        595                 600                 605 

ctg ggc ctg cgg gtg ttc gag aag ggc ctg tcg gcc gcc tac ttc gag     1872 
Leu Gly Leu Arg Val Phe Glu Lys Gly Leu Ser Ala Ala Tyr Phe Glu 
    610                 615                 620 

cgc agc tac ggc aag ggg gtg atg ccc gat acc ttc atc gat ttc aag     1920 
Arg Ser Tyr Gly Lys Gly Val Met Pro Asp Thr Phe Ile Asp Phe Lys 
625                 630                 635                 640 

aag cag cgc ttc cgc tgg gcc tac ggc gcg atc cag atc atg aag cgg     1968 
Lys Gln Arg Phe Arg Trp Ala Tyr Gly Ala Ile Gln Ile Met Lys Arg 
                645                 650                 655 

cat acc gac gcc ctg ctg cgc ggc cgc ggt ccc gac ggc agc cgc ctg     2016 
His Thr Asp Ala Leu Leu Arg Gly Arg Gly Pro Asp Gly Ser Arg Leu 
            660                 665                 670 

acc cgc ggc cag cgc tac cac ttc gtg gcc ggc tgg ctg ccg tgg atc     2064 
Thr Arg Gly Gln Arg Tyr His Phe Val Ala Gly Trp Leu Pro Trp Ile 
        675                 680                 685 

gcc gac ggc ctg aac atc ttc ttc acc ctc ggc gcg ctg ctc tgg tcg     2112 
Ala Asp Gly Leu Asn Ile Phe Phe Thr Leu Gly Ala Leu Leu Trp Ser 
    690                 695                 700 

gcg gcg atg atc atc gtg ccc aag cgc gtc gac ccg ccg ctg ctg atc     2160 
Ala Ala Met Ile Ile Val Pro Lys Arg Val Asp Pro Pro Leu Leu Ile 
705                 710                 715                 720 

ttc gcg atc ctg ccg ctg gcc ctg ttc gtc ttc aag gtc ggc aag atc     2208 
Phe Ala Ile Leu Pro Leu Ala Leu Phe Val Phe Lys Val Gly Lys Ile 
                725                 730                 735 

ctc ttc ctc tac cgg cgc acc gtc ggc gtc gac ctg cgc gac tcg ttc     2256 
Leu Phe Leu Tyr Arg Arg Thr Val Gly Val Asp Leu Arg Asp Ser Phe 
            740                 745                 750 

ttc gcc gcc ctc gcc ggc ctg tcg ctc tcg cac acc att gcc aag gcg     2304 
Phe Ala Ala Leu Ala Gly Leu Ser Leu Ser His Thr Ile Ala Lys Ala 
        755                 760                 765 

gtg ctg tac ggc ttc gtc acc cgc ggc atc ccg ttc ttc cgc acg ccg     2352 
Val Leu Tyr Gly Phe Val Thr Arg Gly Ile Pro Phe Phe Arg Thr Pro 
    770                 775                 780 

aag atg cgc tcc agc cac ggc ctg ctg gtg gcc ctg gcg gag gcc cgc     2400 
Lys Met Arg Ser Ser His Gly Leu Leu Val Ala Leu Ala Glu Ala Arg 
785                 790                 795                 800 

gag gaa gtc ttc gtg atg ctc ctg ctg tgg ggc gcg gcg gcc ggc atc     2448 
Glu Glu Val Phe Val Met Leu Leu Leu Trp Gly Ala Ala Ala Gly Ile 
                805                 810                 815 

gtg gcg gtt cag ggc gtg ccg agc cgc gac ctg ctg atc tgg gtc gcc     2496 
Val Ala Val Gln Gly Val Pro Ser Arg Asp Leu Leu Ile Trp Val Ala 
            820                 825                 830 

atg ctc ctg gtg caa tcg ctg ccc tac ctg gcg gcg ctg gtc atg gcc     2544 
Met Leu Leu Val Gln Ser Leu Pro Tyr Leu Ala Ala Leu Val Met Ala 
        835                 840                 845 

ttg ctc tcg tcg ctg ccg aaa ccg cgc gag gaa ctg gcc ggc ggc gcc     2592 
Leu Leu Ser Ser Leu Pro Lys Pro Arg Glu Glu Leu Ala Gly Gly Ala 
    850                 855                 860 

gag cag atc ggc ggt tga                                             2610 
Glu Gln Ile Gly Gly 
865 

 
           
             2  
             869  
             PRT  
             Pseudomonas aeruginosa  
           
            2 

Met Ser Ser Arg Lys Ile Gly Leu Asn Leu Val Val Ile Val Ala Leu 
 1               5                  10                  15 

Ala Ala Leu Phe Thr Gly Ile Trp Ala Leu Tyr Asn Arg Pro Val Ser 
            20                  25                  30 

Val Pro Asp Trp Pro Glu Arg Ile Ser Gly Phe Ser Phe Ser Pro Phe 
        35                  40                  45 

Arg Leu Asn Gln Asn Pro Gln Ser Gly Arg Tyr Pro Ser Ala Glu Gln 
    50                  55                  60 

Met Arg Thr Asp Leu Glu Leu Val Ala Arg His Thr His Ser Ile Arg 
65                  70                  75                  80 

Thr Tyr Ser Val Gln Gly Ala Leu Gly Asp Ile Pro Ala Leu Ala Glu 
                85                  90                  95 

Ala Phe Gly Leu Arg Val Ser Leu Gly Ile Trp Leu Gly Pro Asp Leu 
            100                 105                 110 

Ala Ser Asn Glu Ala Glu Ile Ala Arg Ala Ile Arg Ile Ala Asn Glu 
        115                 120                 125 

Ser Pro Ser Val Val Arg Val Ile Val Gly Asn Glu Ala Leu Phe Arg 
    130                 135                 140 

Arg Glu Val Thr Ala Glu Gln Leu Ile Ala Tyr Leu Asp Arg Val Arg 
145                 150                 155                 160 

Ala Ala Val Lys Val Pro Val Thr Thr Ala Glu Gln Trp His Val Tyr 
                165                 170                 175 

Arg Glu His Pro Glu Leu Ala Gln His Val Asp Leu Ile Ala Ala His 
            180                 185                 190 

Val Leu Pro Tyr Trp Glu Ala Thr Pro Val Ala Asp Ala Val Asp Phe 
        195                 200                 205 

Val Leu Glu Arg Ala Arg Glu Leu Lys Ala Ala Phe Pro Arg Lys Pro 
    210                 215                 220 

Leu Leu Leu Ala Glu Val Gly Trp Pro Ser Asn Gly Arg Met Arg Gly 
225                 230                 235                 240 

Ser Ala Glu Ala Thr Pro Ala Asp Gln Ala Ile Tyr Leu Arg Arg Leu 
                245                 250                 255 

Thr Asn Ala Leu Asn Gly Glu Gly Tyr Ser Tyr Phe Val Ile Glu Ala 
            260                 265                 270 

Phe Asp Gln Pro Trp Lys Val Ser Ala Glu Gly Ser Val Gly Ala Tyr 
        275                 280                 285 

Trp Gly Val Tyr Asn Ala Asp Arg Lys Ala Lys Phe Asn Phe Thr Gly 
    290                 295                 300 

Pro Val Val Pro Ile Pro Lys Trp Arg Ala Leu Ala Ile Ala Ser Ala 
305                 310                 315                 320 

Val Leu Ala Val Leu Ala Phe Thr Leu Leu Leu Ile Asp Ser Ser Ser 
                325                 330                 335 

Leu Arg Gln Arg Gly Arg Thr Phe Leu Ala Val Val Ser Phe Ala Cys 
            340                 345                 350 

Ala Ser Val Leu Val Trp Ile Ala Tyr Asp Tyr Ser Gln Gln Tyr Ser 
        355                 360                 365 

Thr Trp Phe Ser Leu Thr Val Gly Ala Leu Leu Gly Val Gly Ala Leu 
    370                 375                 380 

Gly Val Val Ile Val Leu Phe Thr Glu Ala His Glu Leu Ala Glu Ala 
385                 390                 395                 400 

Val Trp Thr Arg Lys Arg Arg Arg Pro Phe Leu Pro Ile Thr Ala Ala 
                405                 410                 415 

Arg Ala Tyr Arg Pro Lys Val Ser Ile His Val Pro Cys Tyr Asn Glu 
            420                 425                 430 

Pro Pro Glu Leu Leu Lys Gln Thr Leu Asp Ala Leu Ala Arg Leu Asp 
        435                 440                 445 

Tyr Pro Asp Tyr Glu Val Leu Val Ile Asp Asn Asn Thr Arg Asp Pro 
    450                 455                 460 

Ala Val Trp Gln Pro Val Glu Ala His Cys Ala Arg Leu Gly Glu Arg 
465                 470                 475                 480 

Phe Arg Phe Phe His Val Ala Pro Leu Glu Gly Phe Lys Ala Gly Ala 
                485                 490                 495 

Leu Asn Phe Ala Leu Gly His Val Ala Ala Asp Val Glu Val Val Ala 
            500                 505                 510 

Val Ile Asp Ala Asp Tyr Cys Val Asp Pro Asp Trp Leu Arg His Met 
        515                 520                 525 

Val Pro His Phe Gly Asp Pro Arg Ile Ala Val Val Gln Ser Pro Gln 
    530                 535                 540 

Asp Tyr Arg Asp Gln His Glu Ser Ala Phe Lys Arg Leu Cys Tyr Ala 
545                 550                 555                 560 

Glu Tyr Lys Gly Phe Phe His Ile Gly Met Val Thr Arg Asn Asp Arg 
                565                 570                 575 

Asp Ala Ile Ile Glu His Gly Thr Met Thr Met Ile Arg Arg Ser Val 
            580                 585                 590 

Leu Asp Glu Leu Arg Trp Pro Glu Trp Cys Ile Thr Glu Asp Ala Glu 
        595                 600                 605 

Leu Gly Leu Arg Val Phe Glu Lys Gly Leu Ser Ala Ala Tyr Phe Glu 
    610                 615                 620 

Arg Ser Tyr Gly Lys Gly Val Met Pro Asp Thr Phe Ile Asp Phe Lys 
625                 630                 635                 640 

Lys Gln Arg Phe Arg Trp Ala Tyr Gly Ala Ile Gln Ile Met Lys Arg 
                645                 650                 655 

His Thr Asp Ala Leu Leu Arg Gly Arg Gly Pro Asp Gly Ser Arg Leu 
            660                 665                 670 

Thr Arg Gly Gln Arg Tyr His Phe Val Ala Gly Trp Leu Pro Trp Ile 
        675                 680                 685 

Ala Asp Gly Leu Asn Ile Phe Phe Thr Leu Gly Ala Leu Leu Trp Ser 
    690                 695                 700 

Ala Ala Met Ile Ile Val Pro Lys Arg Val Asp Pro Pro Leu Leu Ile 
705                 710                 715                 720 

Phe Ala Ile Leu Pro Leu Ala Leu Phe Val Phe Lys Val Gly Lys Ile 
                725                 730                 735 

Leu Phe Leu Tyr Arg Arg Thr Val Gly Val Asp Leu Arg Asp Ser Phe 
            740                 745                 750 

Phe Ala Ala Leu Ala Gly Leu Ser Leu Ser His Thr Ile Ala Lys Ala 
        755                 760                 765 

Val Leu Tyr Gly Phe Val Thr Arg Gly Ile Pro Phe Phe Arg Thr Pro 
    770                 775                 780 

Lys Met Arg Ser Ser His Gly Leu Leu Val Ala Leu Ala Glu Ala Arg 
785                 790                 795                 800 

Glu Glu Val Phe Val Met Leu Leu Leu Trp Gly Ala Ala Ala Gly Ile 
                805                 810                 815 

Val Ala Val Gln Gly Val Pro Ser Arg Asp Leu Leu Ile Trp Val Ala 
            820                 825                 830 

Met Leu Leu Val Gln Ser Leu Pro Tyr Leu Ala Ala Leu Val Met Ala 
        835                 840                 845 

Leu Leu Ser Ser Leu Pro Lys Pro Arg Glu Glu Leu Ala Gly Gly Ala 
    850                 855                 860 

Glu Gln Ile Gly Gly 
865 

 
           
             3  
             7407  
             DNA  
             Pseudomonas aeruginosa  
             
               CDS  
               (1)...(7404)  
             
           
            3 

atg tcg atc cag gcg aaa gtt acc cct atc gat cag agt att tct tct       48 
Met Ser Ile Gln Ala Lys Val Thr Pro Ile Asp Gln Ser Ile Ser Ser 
 1               5                   10                  15 

gcg gct gcc gtc gag gtt ccg gaa aac ggg ata ctc aaa ctc tcc cag       96 
Ala Ala Ala Val Glu Val Pro Glu Asn Gly Ile Leu Lys Leu Ser Gln 
             20                  25                  30 

agc agt aat gtc gcg ctc gat gtc gca ccg gag tcg gtg gcg gga tac      144 
Ser Ser Asn Val Ala Leu Asp Val Ala Pro Glu Ser Val Ala Gly Tyr 
         35                  40                  45 

tcg aag agc ggt tcg gac ctg atc gtc cag ctg aag acc ggg gaa agc      192 
Ser Lys Ser Gly Ser Asp Leu Ile Val Gln Leu Lys Thr Gly Glu Ser 
     50                  55                  60 

gtc cgg atc gcc aac ttc tat gcg gaa ggc cag cct tcc agc caa ctg      240 
Val Arg Ile Ala Asn Phe Tyr Ala Glu Gly Gln Pro Ser Ser Gln Leu 
 65                  70                  75                  80 

ttc ctg gcc gac aag gac aag ctg gtg gcg gta gat ctg ccg ccg gtc      288 
Phe Leu Ala Asp Lys Asp Lys Leu Val Ala Val Asp Leu Pro Pro Val 
                 85                  90                  95 

gct gcc gac ggg ccg ctg atg gcc ggc tac atc ccg cag gaa agc ctg      336 
Ala Ala Asp Gly Pro Leu Met Ala Gly Tyr Ile Pro Gln Glu Ser Leu 
            100                 105                 110 

gcc ggt ttc gag tcg ctg acc ggc gcc ggt gtg ctc ggt ggc atg agc      384 
Ala Gly Phe Glu Ser Leu Thr Gly Ala Gly Val Leu Gly Gly Met Ser 
        115                 120                 125 

gca ggg act gcg ctg ctg gtc ggt gcg gcg gcc atc ggc gcc ggg gtg      432 
Ala Gly Thr Ala Leu Leu Val Gly Ala Ala Ala Ile Gly Ala Gly Val 
    130                 135                 140 

gcg att tcc aac agc agc ggc ggc ggt ggc ggc ggc ggt tct tcg gtg      480 
Ala Ile Ser Asn Ser Ser Gly Gly Gly Gly Gly Gly Gly Ser Ser Val 
145                 150                 155                 160 

ccc ccg gac acc act ccg ccg aag gcg gcc agc ggc ctg aag ata gcg      528 
Pro Pro Asp Thr Thr Pro Pro Lys Ala Ala Ser Gly Leu Lys Ile Ala 
                165                 170                 175 

cct gac ggc agc agc atc agc ggc cag gcc gag gcc ggc gcg agc gtc      576 
Pro Asp Gly Ser Ser Ile Ser Gly Gln Ala Glu Ala Gly Ala Ser Val 
            180                 185                 190 

ggc atc gat acc aat ggc gac ggc aag ccg gac ctc acc gtg atc gcc      624 
Gly Ile Asp Thr Asn Gly Asp Gly Lys Pro Asp Leu Thr Val Ile Ala 
        195                 200                 205 

gat gcc aac ggc aat ttc acc gct ccg ctg aac ccg ccg ctg acc aat      672 
Asp Ala Asn Gly Asn Phe Thr Ala Pro Leu Asn Pro Pro Leu Thr Asn 
    210                 215                 220 

ggc cag acg gtc acc gtg gtg gtc acc gac ccg gct ggc aac gcc agc      720 
Gly Gln Thr Val Thr Val Val Val Thr Asp Pro Ala Gly Asn Ala Ser 
225                 230                 235                 240 

ccg ccg gcc cag gtc acc gct ccg gac act acc gcc ccg gcg ccg gct      768 
Pro Pro Ala Gln Val Thr Ala Pro Asp Thr Thr Ala Pro Ala Pro Ala 
                245                 250                 255 

acc gac gtg cag gtg gcg ccg gac ggc agc agc gtc acc ggc aag gcc      816 
Thr Asp Val Gln Val Ala Pro Asp Gly Ser Ser Val Thr Gly Lys Ala 
            260                 265                 270 

gaa ccc ggc tcg acg gtg ggc gtc gat acc gac ggc gac ggc cag ccg      864 
Glu Pro Gly Ser Thr Val Gly Val Asp Thr Asp Gly Asp Gly Gln Pro 
        275                 280                 285 

gac acc acc gtg gtg gtc ggc ccc ggc ggc agc ttc gag gtt ccg ctg      912 
Asp Thr Thr Val Val Val Gly Pro Gly Gly Ser Phe Glu Val Pro Leu 
    290                 295                 300 

aac ccg ccg ctg acc aat ggc gag acg gtg acg gtg atc gtt acc gac      960 
Asn Pro Pro Leu Thr Asn Gly Glu Thr Val Thr Val Ile Val Thr Asp 
305                 310                 315                 320 

ccg gcc ggc aac aac agc acc ccg gtg acc gtc gag gcg ccg gac acc     1008 
Pro Ala Gly Asn Asn Ser Thr Pro Val Thr Val Glu Ala Pro Asp Thr 
                325                 330                 335 

acc gcc ccg gcg ccg gcc acc gac gtg cag gtg gcg ccg gac ggc agc     1056 
Thr Ala Pro Ala Pro Ala Thr Asp Val Gln Val Ala Pro Asp Gly Ser 
            340                 345                 350 

agc gtc acc ggc aac gca gag ccg ggc gcc acc gtc ggt gtc gac acc     1104 
Ser Val Thr Gly Asn Ala Glu Pro Gly Ala Thr Val Gly Val Asp Thr 
        355                 360                 365 

gat ggc gac ggc cag ccg gac acc acc gtg gtg gtc ggt ccc ggc ggc     1152 
Asp Gly Asp Gly Gln Pro Asp Thr Thr Val Val Val Gly Pro Gly Gly 
    370                 375                 380 

agc ttc gag gtt ccg ctg aac ccg ccg ctg acc aat ggc gag acg gtg     1200 
Ser Phe Glu Val Pro Leu Asn Pro Pro Leu Thr Asn Gly Glu Thr Val 
385                 390                 395                 400 

acg gtg atc gtt acc gac ccg gcc ggc aac agc agc acc ccg gtc acc     1248 
Thr Val Ile Val Thr Asp Pro Ala Gly Asn Ser Ser Thr Pro Val Thr 
                405                 410                 415 

gcc gaa gcc ccc gac ttc ccc gac gcg ccc cag gtc aat gcc agc aac     1296 
Ala Glu Ala Pro Asp Phe Pro Asp Ala Pro Gln Val Asn Ala Ser Asn 
            420                 425                 430 

ggc agc gtc ctc agt ggt acg gcg gaa gcg ggc gtg acc atc gtg atc     1344 
Gly Ser Val Leu Ser Gly Thr Ala Glu Ala Gly Val Thr Ile Val Ile 
        435                 440                 445 

acc gac ggc aac ggc aat ccg atc ggc cag acc agc gcc gat gcc aac     1392 
Thr Asp Gly Asn Gly Asn Pro Ile Gly Gln Thr Ser Ala Asp Ala Asn 
    450                 455                 460 

ggc aac tgg agc ttc acc ccc ggt agc caa ctg ccg gat ggc acc gtg     1440 
Gly Asn Trp Ser Phe Thr Pro Gly Ser Gln Leu Pro Asp Gly Thr Val 
465                 470                 475                 480 

gtc aat gtg gtg gcc agg gac gcc gcc ggc aac agc agc ccg gcg acc     1488 
Val Asn Val Val Ala Arg Asp Ala Ala Gly Asn Ser Ser Pro Ala Thr 
                485                 490                 495 

tcc atc acc gtc gac ggc gtg gcg ccg aac gcg ccg gtg gtc gag ccg     1536 
Ser Ile Thr Val Asp Gly Val Ala Pro Asn Ala Pro Val Val Glu Pro 
            500                 505                 510 

agc aac ggc agc gaa ctc agc ggg act gcc gaa ccg ggc agc agc gtg     1584 
Ser Asn Gly Ser Glu Leu Ser Gly Thr Ala Glu Pro Gly Ser Ser Val 
        515                 520                 525 

acc ctg acc gac ggc aat ggc aat ccg atc ggc cag acc acc gcc gat     1632 
Thr Leu Thr Asp Gly Asn Gly Asn Pro Ile Gly Gln Thr Thr Ala Asp 
    530                 535                 540 

gcc aac ggc aac tgg tct ttc acg ccg tcc acc ccg ttg ccg gac ggt     1680 
Ala Asn Gly Asn Trp Ser Phe Thr Pro Ser Thr Pro Leu Pro Asp Gly 
545                 550                 555                 560 

acc gtg gtc aac gtg gtg gcc agg gat gcc gcc ggc aac agc agt ccg     1728 
Thr Val Val Asn Val Val Ala Arg Asp Ala Ala Gly Asn Ser Ser Pro 
                565                 570                 575 

ccg gcc agc gtt acc gtg gat gcc gtc gcg ccg gcc acg ccc acc gtc     1776 
Pro Ala Ser Val Thr Val Asp Ala Val Ala Pro Ala Thr Pro Thr Val 
            580                 585                 590 

gat ccg agc aac ggt acg acc ctc agc ggc acc gcc gag ccg ggc agt     1824 
Asp Pro Ser Asn Gly Thr Thr Leu Ser Gly Thr Ala Glu Pro Gly Ser 
        595                 600                 605 

agc gtg acc ctg acc gac ggc aac ggt aac ccg ata ggg cag gtc acc     1872 
Ser Val Thr Leu Thr Asp Gly Asn Gly Asn Pro Ile Gly Gln Val Thr 
    610                 615                 620 

gcc gac ggc agc ggc aac tgg acc ttc acc ccg agc acg ccg ttg ccc     1920 
Ala Asp Gly Ser Gly Asn Trp Thr Phe Thr Pro Ser Thr Pro Leu Pro 
625                 630                 635                 640 

aac ggc acg gtg gtc aac gcc acg gct acc gac ccg tcc ggc aac gcc     1968 
Asn Gly Thr Val Val Asn Ala Thr Ala Thr Asp Pro Ser Gly Asn Ala 
                645                 650                 655 

agt tcg ccg gcc agc gtc acc gtg gac gcc gtg gca ccg gcc acg cca     2016 
Ser Ser Pro Ala Ser Val Thr Val Asp Ala Val Ala Pro Ala Thr Pro 
            660                 665                 670 

gtg gtc aac ccg agc aac ggc acc acg ctc agc ggc acc gcc gag ccg     2064 
Val Val Asn Pro Ser Asn Gly Thr Thr Leu Ser Gly Thr Ala Glu Pro 
        675                 680                 685 

ggc gcc acc gtg acc ctg acc gat ggc aac ggc aat ccc atc ggg cag     2112 
Gly Ala Thr Val Thr Leu Thr Asp Gly Asn Gly Asn Pro Ile Gly Gln 
    690                 695                 700 

gtc acc gcc gat ggc agc ggc aac tgg agc ttc act ccg acc acg ccg     2160 
Val Thr Ala Asp Gly Ser Gly Asn Trp Ser Phe Thr Pro Thr Thr Pro 
705                 710                 715                 720 

ttg ccc aac ggc acc gtg gtc aac gcc acg gcc acc gac gcc tcc ggc     2208 
Leu Pro Asn Gly Thr Val Val Asn Ala Thr Ala Thr Asp Ala Ser Gly 
                725                 730                 735 

aac acc agt gcg ggc agc agt gtc acc gtg gac tcg gta gcc ccg gcc     2256 
Asn Thr Ser Ala Gly Ser Ser Val Thr Val Asp Ser Val Ala Pro Ala 
            740                 745                 750 

acg cca gtg atc aac ccc agc aac ggc acc acg ctc agc ggc acc gcc     2304 
Thr Pro Val Ile Asn Pro Ser Asn Gly Thr Thr Leu Ser Gly Thr Ala 
        755                 760                 765 

gag ccg ggc agc agc gtg act ctg acc gat ggc aac ggc aac ccg att     2352 
Glu Pro Gly Ser Ser Val Thr Leu Thr Asp Gly Asn Gly Asn Pro Ile 
    770                 775                 780 

ggc cag gtc acc gcc gac ggc agc ggc aac tgg agc ttc acc ccg tcc     2400 
Gly Gln Val Thr Ala Asp Gly Ser Gly Asn Trp Ser Phe Thr Pro Ser 
785                 790                 795                 800 

acg ccg ctg gcg gat gga acc gtg gtc aac gcc acg gcc acc gat ccg     2448 
Thr Pro Leu Ala Asp Gly Thr Val Val Asn Ala Thr Ala Thr Asp Pro 
                805                 810                 815 

gcg ggc aac acc agc ggc cag ggc agc acc acc gtc gat ggc gtg gcg     2496 
Ala Gly Asn Thr Ser Gly Gln Gly Ser Thr Thr Val Asp Gly Val Ala 
            820                 825                 830 

ccg acc acg ccg acc gtc aac ctg agc aac ggc agc agc ctc agc ggc     2544 
Pro Thr Thr Pro Thr Val Asn Leu Ser Asn Gly Ser Ser Leu Ser Gly 
        835                 840                 845 

act gcg gaa ccg ggc agc acg gtg atc ctc acc gac ggc aac ggc aat     2592 
Thr Ala Glu Pro Gly Ser Thr Val Ile Leu Thr Asp Gly Asn Gly Asn 
    850                 855                 860 

ccg atc gcc gag gtc acc gcc gac ggc agc ggc aac tgg acc tac acc     2640 
Pro Ile Ala Glu Val Thr Ala Asp Gly Ser Gly Asn Trp Thr Tyr Thr 
865                 870                 875                 880 

ccg tcc acg ccg atc gcc aac ggc acc gtg gtc aac gtg gtg gcc cag     2688 
Pro Ser Thr Pro Ile Ala Asn Gly Thr Val Val Asn Val Val Ala Gln 
                885                 890                 895 

gac gcc gcc ggc aat agc agc ccg ggc gcc agc gtc acc gtg gac tcg     2736 
Asp Ala Ala Gly Asn Ser Ser Pro Gly Ala Ser Val Thr Val Asp Ser 
            900                 905                 910 

cag gcc ccg gcg gct ccg gtg gtc aac ccg agc aac ggc act acg ctc     2784 
Gln Ala Pro Ala Ala Pro Val Val Asn Pro Ser Asn Gly Thr Thr Leu 
        915                 920                 925 

agc ggc acc gcc gag ccg ggc gct acc gtg acc ctg acc gac ggc aac     2832 
Ser Gly Thr Ala Glu Pro Gly Ala Thr Val Thr Leu Thr Asp Gly Asn 
    930                 935                 940 

ggc aac ccg att ggc cag gtc acc gcc gac ggc agc ggc aac tgg agc     2880 
Gly Asn Pro Ile Gly Gln Val Thr Ala Asp Gly Ser Gly Asn Trp Ser 
945                 950                 955                 960 

ttc aca ccg ggc acg ccg ctg gcc aac ggc acc gtg gtc aac gcc acg     2928 
Phe Thr Pro Gly Thr Pro Leu Ala Asn Gly Thr Val Val Asn Ala Thr 
                965                 970                 975 

gcc agc gac ccg acc ggc aat acc agc gct ccg gcc agc acc acc gtg     2976 
Ala Ser Asp Pro Thr Gly Asn Thr Ser Ala Pro Ala Ser Thr Thr Val 
            980                 985                 990 

gac tcg gtg gcg ccg gcc gcg ccg gtg gtc aat ccg agc aac ggc gcg     3024 
Asp Ser Val Ala Pro Ala Ala Pro Val Val Asn Pro Ser Asn Gly Ala 
         995                1000                1005 

gag atc agc ggc acc gcc gaa ccg ggc gcc acc gtg acc ctg acc gat     3072 
Glu Ile Ser Gly Thr Ala Glu Pro Gly Ala Thr Val Thr Leu Thr Asp 
    1010                1015                1020 

ggc agc ggc aat ccg atc ggg cag gtc acc gcc gac ggc agc ggc aac     3120 
Gly Ser Gly Asn Pro Ile Gly Gln Val Thr Ala Asp Gly Ser Gly Asn 
1025                1030                1035                1040 

tgg agc ttc acc ccg tcc acg ccg ctg gcg gat gga acc gtg gtc aac     3168 
Trp Ser Phe Thr Pro Ser Thr Pro Leu Ala Asp Gly Thr Val Val Asn 
                1045                1050                1055 

gcc acc gct acc gac ccg gcc ggc aat acc ggc ggc cag ggc agc acc     3216 
Ala Thr Ala Thr Asp Pro Ala Gly Asn Thr Gly Gly Gln Gly Ser Thr 
            1060                1065                1070 

acc gtg gac gcc atc gcg ccg gcc acg ccg acc gtc aac ctg agc aat     3264 
Thr Val Asp Ala Ile Ala Pro Ala Thr Pro Thr Val Asn Leu Ser Asn 
        1075                1080                1085 

ggc agc agc ctc agc ggc acc gcc gag ccg ggc agc acg gtg att ctc     3312 
Gly Ser Ser Leu Ser Gly Thr Ala Glu Pro Gly Ser Thr Val Ile Leu 
    1090                1095                1100 

acc gac ggc aac ggc aat ccg atc gcc gag gtc acc gcc gac ggc agc     3360 
Thr Asp Gly Asn Gly Asn Pro Ile Ala Glu Val Thr Ala Asp Gly Ser 
1105                1110                1115                1120 

ggc aac tgg acc tac acc ccg tcc acg ccg atc gcc aac ggt act gtg     3408 
Gly Asn Trp Thr Tyr Thr Pro Ser Thr Pro Ile Ala Asn Gly Thr Val 
                1125                1130                1135 

gtc aac gtg gtg gcc cag gac gcc tcc ggt aac agc agc ccg ccg gcg     3456 
Val Asn Val Val Ala Gln Asp Ala Ser Gly Asn Ser Ser Pro Pro Ala 
            1140                1145                1150 

acg gtg acc gtc gat tcc agc gcg ccg ccg gcg ccg gtg atc aac ccg     3504 
Thr Val Thr Val Asp Ser Ser Ala Pro Pro Ala Pro Val Ile Asn Pro 
        1155                1160                1165 

agc aac ggc gtc gtc atc agc ggc acc gcc gag gcc ggt gcc acg gtg     3552 
Ser Asn Gly Val Val Ile Ser Gly Thr Ala Glu Ala Gly Ala Thr Val 
    1170                1175                1180 

acc ctc acc gat gcc ggc ggc aac ccg ata ggg cag gtc acc gcc gac     3600 
Thr Leu Thr Asp Ala Gly Gly Asn Pro Ile Gly Gln Val Thr Ala Asp 
1185                1190                1195                1200 

ggc agc ggc aac tgg agc ttc acg ccg ggc acc ccg ctg gcc aac ggc     3648 
Gly Ser Gly Asn Trp Ser Phe Thr Pro Gly Thr Pro Leu Ala Asn Gly 
                1205                1210                1215 

acg gtg atc gtc gcc acg gcc acc gac ccg acc ggc aat acc ggc ccg     3696 
Thr Val Ile Val Ala Thr Ala Thr Asp Pro Thr Gly Asn Thr Gly Pro 
            1220                1225                1230 

cag gcc gcc acc acg gtg gac gcg gtg gcg ccg ccg gcg ccg gtg atc     3744 
Gln Ala Ala Thr Thr Val Asp Ala Val Ala Pro Pro Ala Pro Val Ile 
        1235                1240                1245 

gat ccg agc aac ggc acg acc atc agc ggc acc gcg gag gcc ggg gcc     3792 
Asp Pro Ser Asn Gly Thr Thr Ile Ser Gly Thr Ala Glu Ala Gly Ala 
    1250                1255                1260 

aag gtg atc ctc acc gac ggc aac ggc aac ccg atc ggc gaa acc acc     3840 
Lys Val Ile Leu Thr Asp Gly Asn Gly Asn Pro Ile Gly Glu Thr Thr 
1265                1270                1275                1280 

gcc gac ggc agc ggc aac tgg agc ttc acg ccc ggc acg ccg ctg gcc     3888 
Ala Asp Gly Ser Gly Asn Trp Ser Phe Thr Pro Gly Thr Pro Leu Ala 
                1285                1290                1295 

aac ggc acg gtg gtc aac gcc gtg gcc cag gac cct gcg ggc aat acc     3936 
Asn Gly Thr Val Val Asn Ala Val Ala Gln Asp Pro Ala Gly Asn Thr 
            1300                1305                1310 

ggc ccg cag ggc agc act acc gtg gac gcg gtg gcg ccg aac acg cct     3984 
Gly Pro Gln Gly Ser Thr Thr Val Asp Ala Val Ala Pro Asn Thr Pro 
        1315                1320                1325 

gtg gtc aat ccg agc aac ggc aac ctg ctc aac ggt acc gcc gag ccg     4032 
Val Val Asn Pro Ser Asn Gly Asn Leu Leu Asn Gly Thr Ala Glu Pro 
    1330                1335                1340 

ggc agc acc gtg acc ttg acc gac ggc aac ggc aac ccg atc ggc cag     4080 
Gly Ser Thr Val Thr Leu Thr Asp Gly Asn Gly Asn Pro Ile Gly Gln 
1345                1350                1355                1360 

acc acc gcc gat ggc agc ggc aac tgg agc ttc acg ccc ggc tcg caa     4128 
Thr Thr Ala Asp Gly Ser Gly Asn Trp Ser Phe Thr Pro Gly Ser Gln 
                1365                1370                1375 

ctg ccc aac ggc acc gtg gtc aac gtg acc gcg agc gac gcc gcc ggc     4176 
Leu Pro Asn Gly Thr Val Val Asn Val Thr Ala Ser Asp Ala Ala Gly 
            1380                1385                1390 

aat acc agc ctt ccc gct acc acg acg gtg gat tcc tcg ctg ccg tcg     4224 
Asn Thr Ser Leu Pro Ala Thr Thr Thr Val Asp Ser Ser Leu Pro Ser 
        1395                1400                1405 

atc ccg cag gtg gat ccg agc aac ggt tcg gtg atc agc ggc acc gcg     4272 
Ile Pro Gln Val Asp Pro Ser Asn Gly Ser Val Ile Ser Gly Thr Ala 
    1410                1415                1420 

gac gcc ggc aac acc atc atc atc acc gat ggc aac ggc aac ccg att     4320 
Asp Ala Gly Asn Thr Ile Ile Ile Thr Asp Gly Asn Gly Asn Pro Ile 
1425                1430                1435                1440 

ggc cag gtc acc gcc gac ggc agc ggc aac tgg tcc ttc act cca ggc     4368 
Gly Gln Val Thr Ala Asp Gly Ser Gly Asn Trp Ser Phe Thr Pro Gly 
                1445                1450                1455 

atc ccg ctg ccg gat ggc acg gtg gtc aac gtg gtg gcg cgc agc cca     4416 
Ile Pro Leu Pro Asp Gly Thr Val Val Asn Val Val Ala Arg Ser Pro 
            1460                1465                1470 

agc aat gtc gac agt gcg ccg gcg gtg atc act gtg gat ggc gtg gcc     4464 
Ser Asn Val Asp Ser Ala Pro Ala Val Ile Thr Val Asp Gly Val Ala 
        1475                1480                1485 

ccg gcg gcg ccg gtg atc gat ccg agc aac ggc acc gag ata agc ggt     4512 
Pro Ala Ala Pro Val Ile Asp Pro Ser Asn Gly Thr Glu Ile Ser Gly 
    1490                1495                1500 

acc gcg gag gcc ggc gcg acg gtg atc ctc acc gat ggc ggc ggc aac     4560 
Thr Ala Glu Ala Gly Ala Thr Val Ile Leu Thr Asp Gly Gly Gly Asn 
1505                1510                1515                1520 

ccg atc ggc cag gcc acc gcc gac ggc agc ggc aac tgg acg ttc acc     4608 
Pro Ile Gly Gln Ala Thr Ala Asp Gly Ser Gly Asn Trp Thr Phe Thr 
                1525                1530                1535 

ccg agc acc ccg ctg gcc aac ggc acc gtg atc aac gcc gtg gcc cag     4656 
Pro Ser Thr Pro Leu Ala Asn Gly Thr Val Ile Asn Ala Val Ala Gln 
            1540                1545                1550 

gac ccg gcc ggc aat acc agc ggt ccg gcc agc gtc acc gtc gat gcc     4704 
Asp Pro Ala Gly Asn Thr Ser Gly Pro Ala Ser Val Thr Val Asp Ala 
        1555                1560                1565 

atc gcc ccg ccg gcg ccg gtg atc aat ccg agc aat gga gtc gtc atc     4752 
Ile Ala Pro Pro Ala Pro Val Ile Asn Pro Ser Asn Gly Val Val Ile 
    1570                1575                1580 

agc ggt acg gcg gaa gcc ggg gcc acg gtg atc ctc acc gac ggc aac     4800 
Ser Gly Thr Ala Glu Ala Gly Ala Thr Val Ile Leu Thr Asp Gly Asn 
1585                1590                1595                1600 

ggc aac ccg atc ggc cag gtc acc gcc gac ggc agc ggc aac tgg agc     4848 
Gly Asn Pro Ile Gly Gln Val Thr Ala Asp Gly Ser Gly Asn Trp Ser 
                1605                1610                1615 

ttc acg ccc ggc acg ccg ctg gcc aac ggc tcg gtg atc aat gcg ctg     4896 
Phe Thr Pro Gly Thr Pro Leu Ala Asn Gly Ser Val Ile Asn Ala Leu 
            1620                1625                1630 

gcc cag gac gcc gcc ggc aac aac agc agt ccc acc agc gcc acc gtc     4944 
Ala Gln Asp Ala Ala Gly Asn Asn Ser Ser Pro Thr Ser Ala Thr Val 
        1635                1640                1645 

gac tcg ctg gcg cca gca gcc ccg gtg atc gat ccg agc aac ggt agc     4992 
Asp Ser Leu Ala Pro Ala Ala Pro Val Ile Asp Pro Ser Asn Gly Ser 
    1650                1655                1660 

gtg atc gcc ggt acc gcc gag gct ggt gcc acg gtg atc ctc acc gac     5040 
Val Ile Ala Gly Thr Ala Glu Ala Gly Ala Thr Val Ile Leu Thr Asp 
1665                1670                1675                1680 

ggc aac ggc aac ccg atc ggc cag gtc acc gcc gat ggc agc ggc aac     5088 
Gly Asn Gly Asn Pro Ile Gly Gln Val Thr Ala Asp Gly Ser Gly Asn 
                1685                1690                1695 

tgg agc ttc acg ccc ggc acg ccg ctg tcc aat ggc acg gtg gtc aat     5136 
Trp Ser Phe Thr Pro Gly Thr Pro Leu Ser Asn Gly Thr Val Val Asn 
            1700                1705                1710 

gcg gtg gcc cag gac gct gcc ggc aac acc agc ggc ccg gtc agc acc     5184 
Ala Val Ala Gln Asp Ala Ala Gly Asn Thr Ser Gly Pro Val Ser Thr 
        1715                1720                1725 

acg gtg gac gcg gtg gcc ccg gcc acc ccg gtg atc gac ccg agc aac     5232 
Thr Val Asp Ala Val Ala Pro Ala Thr Pro Val Ile Asp Pro Ser Asn 
    1730                1735                1740 

ggt gtc gaa ctc agc ggc acc gcc gaa ccc ggc gtc cgg gtg atc ctc     5280 
Gly Val Glu Leu Ser Gly Thr Ala Glu Pro Gly Val Arg Val Ile Leu 
1745                1750                1755                1760 

acc gat ggc aat ggc aat ccg atc ggc cag acc ctt gcc gac ggc agc     5328 
Thr Asp Gly Asn Gly Asn Pro Ile Gly Gln Thr Leu Ala Asp Gly Ser 
                1765                1770                1775 

ggc aac tgg agc ttc acg ccg ggc acg ccg ctg gcc aac ggc acg gtg     5376 
Gly Asn Trp Ser Phe Thr Pro Gly Thr Pro Leu Ala Asn Gly Thr Val 
            1780                1785                1790 

gtc aat gcc gtg gcc cag gac ccg gcc ggc aat acc agc ggc ccg gcc     5424 
Val Asn Ala Val Ala Gln Asp Pro Ala Gly Asn Thr Ser Gly Pro Ala 
        1795                1800                1805 

agc acc acg gtg gac acg gtg gct ccg gcc acg ccg gtg atc aat ccc     5472 
Ser Thr Thr Val Asp Thr Val Ala Pro Ala Thr Pro Val Ile Asn Pro 
    1810                1815                1820 

agc aac ggc agc gtg atc acc ggc acc gcc gag gtc ggc gcc aag gtg     5520 
Ser Asn Gly Ser Val Ile Thr Gly Thr Ala Glu Val Gly Ala Lys Val 
1825                1830                1835                1840 

atc ctc acc gat ggc aac ggc aac ccg atc ggc gag acc acc gcc gac     5568 
Ile Leu Thr Asp Gly Asn Gly Asn Pro Ile Gly Glu Thr Thr Ala Asp 
                1845                1850                1855 

ggc agt ggt aac tgg acc ttc acc ccc ggc acg ccg ctg gcc aac ggt     5616 
Gly Ser Gly Asn Trp Thr Phe Thr Pro Gly Thr Pro Leu Ala Asn Gly 
            1860                1865                1870 

acg gtg atc aac gcc gtc gcc gag gac gcc gcg ggc aac gcc agc ggt     5664 
Thr Val Ile Asn Ala Val Ala Glu Asp Ala Ala Gly Asn Ala Ser Gly 
        1875                1880                1885 

ccg gcc agc acc acg gtg gac tcg gtg gcg ccg tcc gct ccg ctg ctg     5712 
Pro Ala Ser Thr Thr Val Asp Ser Val Ala Pro Ser Ala Pro Leu Leu 
    1890                1895                1900 

agc atc agc gcc gac ggc gcg ctg ctg acc ggc acc gcc gag ccg aac     5760 
Ser Ile Ser Ala Asp Gly Ala Leu Leu Thr Gly Thr Ala Glu Pro Asn 
1905                1910                1915                1920 

agc cag gtg cgc atc gtg gtc aac ggc gac acc gcc aac ccg atc acg     5808 
Ser Gln Val Arg Ile Val Val Asn Gly Asp Thr Ala Asn Pro Ile Thr 
                1925                1930                1935 

gtc acc gtc gac ggc gcc ggc aac ttc agc ctg ccg ttc gcg ccg ccg     5856 
Val Thr Val Asp Gly Ala Gly Asn Phe Ser Leu Pro Phe Ala Pro Pro 
            1940                1945                1950 

ctg atc acc ggc gag ctg atc gcc ggg gtc gcc gtc gac gcc gcc ggc     5904 
Leu Ile Thr Gly Glu Leu Ile Ala Gly Val Ala Val Asp Ala Ala Gly 
        1955                1960                1965 

aac gtc agc ggg ccg gcc acc atc aac gcc ccg gac ctg gcg ccg ccg     5952 
Asn Val Ser Gly Pro Ala Thr Ile Asn Ala Pro Asp Leu Ala Pro Pro 
    1970                1975                1980 

acc atc agc gtg ccg gaa gcc gcc gat acc tgg atc aat gcc gcg gag     6000 
Thr Ile Ser Val Pro Glu Ala Ala Asp Thr Trp Ile Asn Ala Ala Glu 
1985                1990                1995                2000 

atc ggc gac ggt atc cag gtc gat gtg acg gtc cgt ccg acc atg cag     6048 
Ile Gly Asp Gly Ile Gln Val Asp Val Thr Val Arg Pro Thr Met Gln 
                2005                2010                2015 

gtc ggc cag gtg gtc acg gtc aag ttc gcc ggg cag aac ggc tac gag     6096 
Val Gly Gln Val Val Thr Val Lys Phe Ala Gly Gln Asn Gly Tyr Glu 
            2020                2025                2030 

gcc gag gtc agc cat acc ctc acc gcc ggc gac atc gcc gcc ggc aac     6144 
Ala Glu Val Ser His Thr Leu Thr Ala Gly Asp Ile Ala Ala Gly Asn 
        2035                2040                2045 

ctg acc ctg acc ctg acg cct ccc ggc ggc atg ggc ccg ttc ccg gag     6192 
Leu Thr Leu Thr Leu Thr Pro Pro Gly Gly Met Gly Pro Phe Pro Glu 
    2050                2055                2060 

ggt gcc tcg acc gtc acc gcc gac atc aac ggc ggc acc gcg tcg acc     6240 
Gly Ala Ser Thr Val Thr Ala Asp Ile Asn Gly Gly Thr Ala Ser Thr 
2065                2070                2075                2080 

ccg gtg ccg ttc acc atc gac acc att ccg ccg gcg acc ccg gtg ctg     6288 
Pro Val Pro Phe Thr Ile Asp Thr Ile Pro Pro Ala Thr Pro Val Leu 
                2085                2090                2095 

tcc ctg gtc ggc aac atc ctg acc atc tcg gcg gag cca ggg acc gag     6336 
Ser Leu Val Gly Asn Ile Leu Thr Ile Ser Ala Glu Pro Gly Thr Glu 
            2100                2105                2110 

ttg acg gtg acc gtc gac gtc ggc ggg gtg acc gcc acc gcc acg gtg     6384 
Leu Thr Val Thr Val Asp Val Gly Gly Val Thr Ala Thr Ala Thr Val 
        2115                2120                2125 

acc gcc gac aac agc ggg ctg gcg tcg ctg aac ctg ctc acc gac ctg     6432 
Thr Ala Asp Asn Ser Gly Leu Ala Ser Leu Asn Leu Leu Thr Asp Leu 
    2130                2135                2140 

gac atc gac ttc agt tgg gac cag ttg ctc aat gcc cag gtg tcg gtg     6480 
Asp Ile Asp Phe Ser Trp Asp Gln Leu Leu Asn Ala Gln Val Ser Val 
2145                2150                2155                2160 

gtc gga cgc gac ccg gcc ggc aac ccg agc aac acg gcg agc atc ggc     6528 
Val Gly Arg Asp Pro Ala Gly Asn Pro Ser Asn Thr Ala Ser Ile Gly 
                2165                2170                2175 

gtc ggc acc agc atc gag caa ccg gtg acc atc ggc aac ttc ggc ctc     6576 
Val Gly Thr Ser Ile Glu Gln Pro Val Thr Ile Gly Asn Phe Gly Leu 
            2180                2185                2190 

gac gtc agc ctc aac ccg ctg aac ccg cgt ttc ggt ttc agc gga acc     6624 
Asp Val Ser Leu Asn Pro Leu Asn Pro Arg Phe Gly Phe Ser Gly Thr 
        2195                2200                2205 

acc gag cct gac tcc agc gtg gtg atc cgg gtc atc acc ccg gcg ttg     6672 
Thr Glu Pro Asp Ser Ser Val Val Ile Arg Val Ile Thr Pro Ala Leu 
    2210                2215                2220 

aac gtc gaa ttg ctg ccg atc cag gcg gat tcg tcc gga aac ttc tcg     6720 
Asn Val Glu Leu Leu Pro Ile Gln Ala Asp Ser Ser Gly Asn Phe Ser 
2225                2230                2235                2240 

ctg aac ctg ctg agc ccg acc atc ctc acc cag ttg ggg ctg aac atc     6768 
Leu Asn Leu Leu Ser Pro Thr Ile Leu Thr Gln Leu Gly Leu Asn Ile 
                2245                2250                2255 

acc gac atc ctc aac ctc ggc tcg cag atc tcg ttc aac ctg gtg tcc     6816 
Thr Asp Ile Leu Asn Leu Gly Ser Gln Ile Ser Phe Asn Leu Val Ser 
            2260                2265                2270 

acc gac tcc aat ggc aac gac agc gcc gcc tac ggg atc acc ctg acc     6864 
Thr Asp Ser Asn Gly Asn Asp Ser Ala Ala Tyr Gly Ile Thr Leu Thr 
        2275                2280                2285 

ccc aac gga ctg tcg ctc aat atc ggc cag atc gat gtc aac ggt act     6912 
Pro Asn Gly Leu Ser Leu Asn Ile Gly Gln Ile Asp Val Asn Gly Thr 
    2290                2295                2300 

tcc ggc gac gac gtg ctg tcc ggc gcc aac ggc agt tcg gag cac atc     6960 
Ser Gly Asp Asp Val Leu Ser Gly Ala Asn Gly Ser Ser Glu His Ile 
2305                2310                2315                2320 

aac ggc ggc gac ggc agc gac ctg atc ttc aac gtg ggc acc ggc gat     7008 
Asn Gly Gly Asp Gly Ser Asp Leu Ile Phe Asn Val Gly Thr Gly Asp 
                2325                2330                2335 

cac gtg gtg gcc ggc aac ggc aac gac acc atc cag atc acc gcg acc     7056 
His Val Val Ala Gly Asn Gly Asn Asp Thr Ile Gln Ile Thr Ala Thr 
            2340                2345                2350 

gat ttc gtc agc atc gat ggc ggc gcc ggg ttc gac acc ctg gtc ctg     7104 
Asp Phe Val Ser Ile Asp Gly Gly Ala Gly Phe Asp Thr Leu Val Leu 
        2355                2360                2365 

gcc aac ggc atc gac ctc gac tac aac gcc gtc ggc gtc ggc acg ctc     7152 
Ala Asn Gly Ile Asp Leu Asp Tyr Asn Ala Val Gly Val Gly Thr Leu 
    2370                2375                2380 

agc aac ctc gag cgc atc gac ctc ggc aag ggc gat tcg ggt agc gtg     7200 
Ser Asn Leu Glu Arg Ile Asp Leu Gly Lys Gly Asp Ser Gly Ser Val 
2385                2390                2395                2400 

ctg acc ctg acc gcg gcg gag gtg gat gcc atc acc gat gcc aac aac     7248 
Leu Thr Leu Thr Ala Ala Glu Val Asp Ala Ile Thr Asp Ala Asn Asn 
                2405                2410                2415 

acg ttg cag atc acc ggc gag aac aac gac acc ctg aac gtg gtg ggc     7296 
Thr Leu Gln Ile Thr Gly Glu Asn Asn Asp Thr Leu Asn Val Val Gly 
            2420                2425                2430 

gcg gtg aat acc ggt acc acg caa ctg atc aac ggc att acc tac gac     7344 
Ala Val Asn Thr Gly Thr Thr Gln Leu Ile Asn Gly Ile Thr Tyr Asp 
        2435                2440                2445 

gtc tac acc ttc ggc agt acc acc ctg ctg atc gag gac aac acg gta     7392 
Val Tyr Thr Phe Gly Ser Thr Thr Leu Leu Ile Glu Asp Asn Thr Val 
    2450                2455                2460 

cag gtc gtg gtc tga                                                 7407 
Gln Val Val Val 
2465 

 
           
             4  
             2468  
             PRT  
             Pseudomonas aeruginosa  
           
            4 

Met Ser Ile Gln Ala Lys Val Thr Pro Ile Asp Gln Ser Ile Ser Ser 
 1               5                  10                  15 

Ala Ala Ala Val Glu Val Pro Glu Asn Gly Ile Leu Lys Leu Ser Gln 
            20                  25                  30 

Ser Ser Asn Val Ala Leu Asp Val Ala Pro Glu Ser Val Ala Gly Tyr 
        35                  40                  45 

Ser Lys Ser Gly Ser Asp Leu Ile Val Gln Leu Lys Thr Gly Glu Ser 
    50                  55                  60 

Val Arg Ile Ala Asn Phe Tyr Ala Glu Gly Gln Pro Ser Ser Gln Leu 
65                  70                  75                  80 

Phe Leu Ala Asp Lys Asp Lys Leu Val Ala Val Asp Leu Pro Pro Val 
                85                  90                  95 

Ala Ala Asp Gly Pro Leu Met Ala Gly Tyr Ile Pro Gln Glu Ser Leu 
            100                 105                 110 

Ala Gly Phe Glu Ser Leu Thr Gly Ala Gly Val Leu Gly Gly Met Ser 
        115                 120                 125 

Ala Gly Thr Ala Leu Leu Val Gly Ala Ala Ala Ile Gly Ala Gly Val 
    130                 135                 140 

Ala Ile Ser Asn Ser Ser Gly Gly Gly Gly Gly Gly Gly Ser Ser Val 
145                 150                 155                 160 

Pro Pro Asp Thr Thr Pro Pro Lys Ala Ala Ser Gly Leu Lys Ile Ala 
                165                 170                 175 

Pro Asp Gly Ser Ser Ile Ser Gly Gln Ala Glu Ala Gly Ala Ser Val 
            180                 185                 190 

Gly Ile Asp Thr Asn Gly Asp Gly Lys Pro Asp Leu Thr Val Ile Ala 
        195                 200                 205 

Asp Ala Asn Gly Asn Phe Thr Ala Pro Leu Asn Pro Pro Leu Thr Asn 
    210                 215                 220 

Gly Gln Thr Val Thr Val Val Val Thr Asp Pro Ala Gly Asn Ala Ser 
225                 230                 235                 240 

Pro Pro Ala Gln Val Thr Ala Pro Asp Thr Thr Ala Pro Ala Pro Ala 
                245                 250                 255 

Thr Asp Val Gln Val Ala Pro Asp Gly Ser Ser Val Thr Gly Lys Ala 
            260                 265                 270 

Glu Pro Gly Ser Thr Val Gly Val Asp Thr Asp Gly Asp Gly Gln Pro 
        275                 280                 285 

Asp Thr Thr Val Val Val Gly Pro Gly Gly Ser Phe Glu Val Pro Leu 
    290                 295                 300 

Asn Pro Pro Leu Thr Asn Gly Glu Thr Val Thr Val Ile Val Thr Asp 
305                 310                 315                 320 

Pro Ala Gly Asn Asn Ser Thr Pro Val Thr Val Glu Ala Pro Asp Thr 
                325                 330                 335 

Thr Ala Pro Ala Pro Ala Thr Asp Val Gln Val Ala Pro Asp Gly Ser 
            340                 345                 350 

Ser Val Thr Gly Asn Ala Glu Pro Gly Ala Thr Val Gly Val Asp Thr 
        355                 360                 365 

Asp Gly Asp Gly Gln Pro Asp Thr Thr Val Val Val Gly Pro Gly Gly 
    370                 375                 380 

Ser Phe Glu Val Pro Leu Asn Pro Pro Leu Thr Asn Gly Glu Thr Val 
385                 390                 395                 400 

Thr Val Ile Val Thr Asp Pro Ala Gly Asn Ser Ser Thr Pro Val Thr 
                405                 410                 415 

Ala Glu Ala Pro Asp Phe Pro Asp Ala Pro Gln Val Asn Ala Ser Asn 
            420                 425                 430 

Gly Ser Val Leu Ser Gly Thr Ala Glu Ala Gly Val Thr Ile Val Ile 
        435                 440                 445 

Thr Asp Gly Asn Gly Asn Pro Ile Gly Gln Thr Ser Ala Asp Ala Asn 
    450                 455                 460 

Gly Asn Trp Ser Phe Thr Pro Gly Ser Gln Leu Pro Asp Gly Thr Val 
465                 470                 475                 480 

Val Asn Val Val Ala Arg Asp Ala Ala Gly Asn Ser Ser Pro Ala Thr 
                485                 490                 495 

Ser Ile Thr Val Asp Gly Val Ala Pro Asn Ala Pro Val Val Glu Pro 
            500                 505                 510 

Ser Asn Gly Ser Glu Leu Ser Gly Thr Ala Glu Pro Gly Ser Ser Val 
        515                 520                 525 

Thr Leu Thr Asp Gly Asn Gly Asn Pro Ile Gly Gln Thr Thr Ala Asp 
    530                 535                 540 

Ala Asn Gly Asn Trp Ser Phe Thr Pro Ser Thr Pro Leu Pro Asp Gly 
545                 550                 555                 560 

Thr Val Val Asn Val Val Ala Arg Asp Ala Ala Gly Asn Ser Ser Pro 
                565                 570                 575 

Pro Ala Ser Val Thr Val Asp Ala Val Ala Pro Ala Thr Pro Thr Val 
            580                 585                 590 

Asp Pro Ser Asn Gly Thr Thr Leu Ser Gly Thr Ala Glu Pro Gly Ser 
        595                 600                 605 

Ser Val Thr Leu Thr Asp Gly Asn Gly Asn Pro Ile Gly Gln Val Thr 
    610                 615                 620 

Ala Asp Gly Ser Gly Asn Trp Thr Phe Thr Pro Ser Thr Pro Leu Pro 
625                 630                 635                 640 

Asn Gly Thr Val Val Asn Ala Thr Ala Thr Asp Pro Ser Gly Asn Ala 
                645                 650                 655 

Ser Ser Pro Ala Ser Val Thr Val Asp Ala Val Ala Pro Ala Thr Pro 
            660                 665                 670 

Val Val Asn Pro Ser Asn Gly Thr Thr Leu Ser Gly Thr Ala Glu Pro 
        675                 680                 685 

Gly Ala Thr Val Thr Leu Thr Asp Gly Asn Gly Asn Pro Ile Gly Gln 
    690                 695                 700 

Val Thr Ala Asp Gly Ser Gly Asn Trp Ser Phe Thr Pro Thr Thr Pro 
705                 710                 715                 720 

Leu Pro Asn Gly Thr Val Val Asn Ala Thr Ala Thr Asp Ala Ser Gly 
                725                 730                 735 

Asn Thr Ser Ala Gly Ser Ser Val Thr Val Asp Ser Val Ala Pro Ala 
            740                 745                 750 

Thr Pro Val Ile Asn Pro Ser Asn Gly Thr Thr Leu Ser Gly Thr Ala 
        755                 760                 765 

Glu Pro Gly Ser Ser Val Thr Leu Thr Asp Gly Asn Gly Asn Pro Ile 
    770                 775                 780 

Gly Gln Val Thr Ala Asp Gly Ser Gly Asn Trp Ser Phe Thr Pro Ser 
785                 790                 795                 800 

Thr Pro Leu Ala Asp Gly Thr Val Val Asn Ala Thr Ala Thr Asp Pro 
                805                 810                 815 

Ala Gly Asn Thr Ser Gly Gln Gly Ser Thr Thr Val Asp Gly Val Ala 
            820                 825                 830 

Pro Thr Thr Pro Thr Val Asn Leu Ser Asn Gly Ser Ser Leu Ser Gly 
        835                 840                 845 

Thr Ala Glu Pro Gly Ser Thr Val Ile Leu Thr Asp Gly Asn Gly Asn 
    850                 855                 860 

Pro Ile Ala Glu Val Thr Ala Asp Gly Ser Gly Asn Trp Thr Tyr Thr 
865                 870                 875                 880 

Pro Ser Thr Pro Ile Ala Asn Gly Thr Val Val Asn Val Val Ala Gln 
                885                 890                 895 

Asp Ala Ala Gly Asn Ser Ser Pro Gly Ala Ser Val Thr Val Asp Ser 
            900                 905                 910 

Gln Ala Pro Ala Ala Pro Val Val Asn Pro Ser Asn Gly Thr Thr Leu 
        915                 920                 925 

Ser Gly Thr Ala Glu Pro Gly Ala Thr Val Thr Leu Thr Asp Gly Asn 
    930                 935                 940 

Gly Asn Pro Ile Gly Gln Val Thr Ala Asp Gly Ser Gly Asn Trp Ser 
945                 950                 955                 960 

Phe Thr Pro Gly Thr Pro Leu Ala Asn Gly Thr Val Val Asn Ala Thr 
                965                 970                 975 

Ala Ser Asp Pro Thr Gly Asn Thr Ser Ala Pro Ala Ser Thr Thr Val 
            980                 985                 990 

Asp Ser Val Ala Pro Ala Ala Pro Val Val Asn Pro Ser Asn Gly Ala 
        995                 1000                1005 

Glu Ile Ser Gly Thr Ala Glu Pro Gly Ala Thr Val Thr Leu Thr Asp 
    1010                1015                1020 

Gly Ser Gly Asn Pro Ile Gly Gln Val Thr Ala Asp Gly Ser Gly Asn 
1025                1030                1035                1040 

Trp Ser Phe Thr Pro Ser Thr Pro Leu Ala Asp Gly Thr Val Val Asn 
                1045                1050                1055 

Ala Thr Ala Thr Asp Pro Ala Gly Asn Thr Gly Gly Gln Gly Ser Thr 
            1060                1065                1070 

Thr Val Asp Ala Ile Ala Pro Ala Thr Pro Thr Val Asn Leu Ser Asn 
        1075                1080                1085 

Gly Ser Ser Leu Ser Gly Thr Ala Glu Pro Gly Ser Thr Val Ile Leu 
    1090                1095                1100 

Thr Asp Gly Asn Gly Asn Pro Ile Ala Glu Val Thr Ala Asp Gly Ser 
1105                1110                1115                1120 

Gly Asn Trp Thr Tyr Thr Pro Ser Thr Pro Ile Ala Asn Gly Thr Val 
                1125                1130                1135 

Val Asn Val Val Ala Gln Asp Ala Ser Gly Asn Ser Ser Pro Pro Ala 
            1140                1145                1150 

Thr Val Thr Val Asp Ser Ser Ala Pro Pro Ala Pro Val Ile Asn Pro 
        1155                1160                1165 

Ser Asn Gly Val Val Ile Ser Gly Thr Ala Glu Ala Gly Ala Thr Val 
    1170                1175                1180 

Thr Leu Thr Asp Ala Gly Gly Asn Pro Ile Gly Gln Val Thr Ala Asp 
1185                1190                1195                1200 

Gly Ser Gly Asn Trp Ser Phe Thr Pro Gly Thr Pro Leu Ala Asn Gly 
                1205                1210                1215 

Thr Val Ile Val Ala Thr Ala Thr Asp Pro Thr Gly Asn Thr Gly Pro 
            1220                1225                1230 

Gln Ala Ala Thr Thr Val Asp Ala Val Ala Pro Pro Ala Pro Val Ile 
        1235                1240                1245 

Asp Pro Ser Asn Gly Thr Thr Ile Ser Gly Thr Ala Glu Ala Gly Ala 
    1250                1255                1260 

Lys Val Ile Leu Thr Asp Gly Asn Gly Asn Pro Ile Gly Glu Thr Thr 
1265                1270                1275                1280 

Ala Asp Gly Ser Gly Asn Trp Ser Phe Thr Pro Gly Thr Pro Leu Ala 
                1285                1290                1295 

Asn Gly Thr Val Val Asn Ala Val Ala Gln Asp Pro Ala Gly Asn Thr 
            1300                1305                1310 

Gly Pro Gln Gly Ser Thr Thr Val Asp Ala Val Ala Pro Asn Thr Pro 
        1315                1320                1325 

Val Val Asn Pro Ser Asn Gly Asn Leu Leu Asn Gly Thr Ala Glu Pro 
    1330                1335                1340 

Gly Ser Thr Val Thr Leu Thr Asp Gly Asn Gly Asn Pro Ile Gly Gln 
1345                1350                1355                1360 

Thr Thr Ala Asp Gly Ser Gly Asn Trp Ser Phe Thr Pro Gly Ser Gln 
                1365                1370                1375 

Leu Pro Asn Gly Thr Val Val Asn Val Thr Ala Ser Asp Ala Ala Gly 
            1380                1385                1390 

Asn Thr Ser Leu Pro Ala Thr Thr Thr Val Asp Ser Ser Leu Pro Ser 
        1395                1400                1405 

Ile Pro Gln Val Asp Pro Ser Asn Gly Ser Val Ile Ser Gly Thr Ala 
    1410                1415                1420 

Asp Ala Gly Asn Thr Ile Ile Ile Thr Asp Gly Asn Gly Asn Pro Ile 
1425                1430                1435                1440 

Gly Gln Val Thr Ala Asp Gly Ser Gly Asn Trp Ser Phe Thr Pro Gly 
                1445                1450                1455 

Ile Pro Leu Pro Asp Gly Thr Val Val Asn Val Val Ala Arg Ser Pro 
            1460                1465                1470 

Ser Asn Val Asp Ser Ala Pro Ala Val Ile Thr Val Asp Gly Val Ala 
        1475                1480                1485 

Pro Ala Ala Pro Val Ile Asp Pro Ser Asn Gly Thr Glu Ile Ser Gly 
    1490                1495                1500 

Thr Ala Glu Ala Gly Ala Thr Val Ile Leu Thr Asp Gly Gly Gly Asn 
1505                1510                1515                1520 

Pro Ile Gly Gln Ala Thr Ala Asp Gly Ser Gly Asn Trp Thr Phe Thr 
                1525                1530                1535 

Pro Ser Thr Pro Leu Ala Asn Gly Thr Val Ile Asn Ala Val Ala Gln 
            1540                1545                1550 

Asp Pro Ala Gly Asn Thr Ser Gly Pro Ala Ser Val Thr Val Asp Ala 
        1555                1560                1565 

Ile Ala Pro Pro Ala Pro Val Ile Asn Pro Ser Asn Gly Val Val Ile 
    1570                1575                1580 

Ser Gly Thr Ala Glu Ala Gly Ala Thr Val Ile Leu Thr Asp Gly Asn 
1585                1590                1595                1600 

Gly Asn Pro Ile Gly Gln Val Thr Ala Asp Gly Ser Gly Asn Trp Ser 
                1605                1610                1615 

Phe Thr Pro Gly Thr Pro Leu Ala Asn Gly Ser Val Ile Asn Ala Leu 
            1620                1625                1630 

Ala Gln Asp Ala Ala Gly Asn Asn Ser Ser Pro Thr Ser Ala Thr Val 
        1635                1640                1645 

Asp Ser Leu Ala Pro Ala Ala Pro Val Ile Asp Pro Ser Asn Gly Ser 
    1650                1655                1660 

Val Ile Ala Gly Thr Ala Glu Ala Gly Ala Thr Val Ile Leu Thr Asp 
1665                1670                1675                1680 

Gly Asn Gly Asn Pro Ile Gly Gln Val Thr Ala Asp Gly Ser Gly Asn 
                1685                1690                1695 

Trp Ser Phe Thr Pro Gly Thr Pro Leu Ser Asn Gly Thr Val Val Asn 
            1700                1705                1710 

Ala Val Ala Gln Asp Ala Ala Gly Asn Thr Ser Gly Pro Val Ser Thr 
        1715                1720                1725 

Thr Val Asp Ala Val Ala Pro Ala Thr Pro Val Ile Asp Pro Ser Asn 
    1730                1735                1740 

Gly Val Glu Leu Ser Gly Thr Ala Glu Pro Gly Val Arg Val Ile Leu 
1745                1750                1755                1760 

Thr Asp Gly Asn Gly Asn Pro Ile Gly Gln Thr Leu Ala Asp Gly Ser 
                1765                1770                1775 

Gly Asn Trp Ser Phe Thr Pro Gly Thr Pro Leu Ala Asn Gly Thr Val 
            1780                1785                1790 

Val Asn Ala Val Ala Gln Asp Pro Ala Gly Asn Thr Ser Gly Pro Ala 
        1795                1800                1805 

Ser Thr Thr Val Asp Thr Val Ala Pro Ala Thr Pro Val Ile Asn Pro 
    1810                1815                1820 

Ser Asn Gly Ser Val Ile Thr Gly Thr Ala Glu Val Gly Ala Lys Val 
1825                1830                1835                1840 

Ile Leu Thr Asp Gly Asn Gly Asn Pro Ile Gly Glu Thr Thr Ala Asp 
                1845                1850                1855 

Gly Ser Gly Asn Trp Thr Phe Thr Pro Gly Thr Pro Leu Ala Asn Gly 
            1860                1865                1870 

Thr Val Ile Asn Ala Val Ala Glu Asp Ala Ala Gly Asn Ala Ser Gly 
        1875                1880                1885 

Pro Ala Ser Thr Thr Val Asp Ser Val Ala Pro Ser Ala Pro Leu Leu 
    1890                1895                1900 

Ser Ile Ser Ala Asp Gly Ala Leu Leu Thr Gly Thr Ala Glu Pro Asn 
1905                1910                1915                1920 

Ser Gln Val Arg Ile Val Val Asn Gly Asp Thr Ala Asn Pro Ile Thr 
                1925                1930                1935 

Val Thr Val Asp Gly Ala Gly Asn Phe Ser Leu Pro Phe Ala Pro Pro 
            1940                1945                1950 

Leu Ile Thr Gly Glu Leu Ile Ala Gly Val Ala Val Asp Ala Ala Gly 
        1955                1960                1965 

Asn Val Ser Gly Pro Ala Thr Ile Asn Ala Pro Asp Leu Ala Pro Pro 
    1970                1975                1980 

Thr Ile Ser Val Pro Glu Ala Ala Asp Thr Trp Ile Asn Ala Ala Glu 
1985                1990                1995                2000 

Ile Gly Asp Gly Ile Gln Val Asp Val Thr Val Arg Pro Thr Met Gln 
                2005                2010                2015 

Val Gly Gln Val Val Thr Val Lys Phe Ala Gly Gln Asn Gly Tyr Glu 
            2020                2025                2030 

Ala Glu Val Ser His Thr Leu Thr Ala Gly Asp Ile Ala Ala Gly Asn 
        2035                2040                2045 

Leu Thr Leu Thr Leu Thr Pro Pro Gly Gly Met Gly Pro Phe Pro Glu 
    2050                2055                2060 

Gly Ala Ser Thr Val Thr Ala Asp Ile Asn Gly Gly Thr Ala Ser Thr 
2065                2070                2075                2080 

Pro Val Pro Phe Thr Ile Asp Thr Ile Pro Pro Ala Thr Pro Val Leu 
                2085                2090                2095 

Ser Leu Val Gly Asn Ile Leu Thr Ile Ser Ala Glu Pro Gly Thr Glu 
            2100                2105                2110 

Leu Thr Val Thr Val Asp Val Gly Gly Val Thr Ala Thr Ala Thr Val 
        2115                2120                2125 

Thr Ala Asp Asn Ser Gly Leu Ala Ser Leu Asn Leu Leu Thr Asp Leu 
    2130                2135                2140 

Asp Ile Asp Phe Ser Trp Asp Gln Leu Leu Asn Ala Gln Val Ser Val 
2145                2150                2155                2160 

Val Gly Arg Asp Pro Ala Gly Asn Pro Ser Asn Thr Ala Ser Ile Gly 
                2165                2170                2175 

Val Gly Thr Ser Ile Glu Gln Pro Val Thr Ile Gly Asn Phe Gly Leu 
            2180                2185                2190 

Asp Val Ser Leu Asn Pro Leu Asn Pro Arg Phe Gly Phe Ser Gly Thr 
        2195                2200                2205 

Thr Glu Pro Asp Ser Ser Val Val Ile Arg Val Ile Thr Pro Ala Leu 
    2210                2215                2220 

Asn Val Glu Leu Leu Pro Ile Gln Ala Asp Ser Ser Gly Asn Phe Ser 
2225                2230                2235                2240 

Leu Asn Leu Leu Ser Pro Thr Ile Leu Thr Gln Leu Gly Leu Asn Ile 
                2245                2250                2255 

Thr Asp Ile Leu Asn Leu Gly Ser Gln Ile Ser Phe Asn Leu Val Ser 
            2260                2265                2270 

Thr Asp Ser Asn Gly Asn Asp Ser Ala Ala Tyr Gly Ile Thr Leu Thr 
        2275                2280                2285 

Pro Asn Gly Leu Ser Leu Asn Ile Gly Gln Ile Asp Val Asn Gly Thr 
    2290                2295                2300 

Ser Gly Asp Asp Val Leu Ser Gly Ala Asn Gly Ser Ser Glu His Ile 
2305                2310                2315                2320 

Asn Gly Gly Asp Gly Ser Asp Leu Ile Phe Asn Val Gly Thr Gly Asp 
                2325                2330                2335 

His Val Val Ala Gly Asn Gly Asn Asp Thr Ile Gln Ile Thr Ala Thr 
            2340                2345                2350 

Asp Phe Val Ser Ile Asp Gly Gly Ala Gly Phe Asp Thr Leu Val Leu 
        2355                2360                2365 

Ala Asn Gly Ile Asp Leu Asp Tyr Asn Ala Val Gly Val Gly Thr Leu 
    2370                2375                2380 

Ser Asn Leu Glu Arg Ile Asp Leu Gly Lys Gly Asp Ser Gly Ser Val 
2385                2390                2395                2400 

Leu Thr Leu Thr Ala Ala Glu Val Asp Ala Ile Thr Asp Ala Asn Asn 
                2405                2410                2415 

Thr Leu Gln Ile Thr Gly Glu Asn Asn Asp Thr Leu Asn Val Val Gly 
            2420                2425                2430 

Ala Val Asn Thr Gly Thr Thr Gln Leu Ile Asn Gly Ile Thr Tyr Asp 
        2435                2440                2445 

Val Tyr Thr Phe Gly Ser Thr Thr Leu Leu Ile Glu Asp Asn Thr Val 
    2450                2455                2460 

Gln Val Val Val 
2465 

 
           
             5  
             1278  
             DNA  
             Pseudomonas aeruginosa  
             
               CDS  
               (1)...(1275)  
             
           
            5 

atg cgc ggg cgc agg cag tac gcg cgc aag gga cgg cgg cat ggg aag       48 
Met Arg Gly Arg Arg Gln Tyr Ala Arg Lys Gly Arg Arg His Gly Lys 
 1               5                   10                  15 

gga gcc atc tgg ctc ctt tcc ctg ggt ctg ccg atg ttc gcg tcg gcc       96 
Gly Ala Ile Trp Leu Leu Ser Leu Gly Leu Pro Met Phe Ala Ser Ala 
             20                  25                  30 

atg ccc ctc gac cag gcg gtc agg gca ggg ctg gcg atc cac ccg gaa      144 
Met Pro Leu Asp Gln Ala Val Arg Ala Gly Leu Ala Ile His Pro Glu 
         35                  40                  45 

gta cga tcc gcg atg gcc gaa gcg gac cgt gca ggc acc gag gtg gag      192 
Val Arg Ser Ala Met Ala Glu Ala Asp Arg Ala Gly Thr Glu Val Glu 
     50                  55                  60 

atg gcc aaa ggg ggg tac tac ccc tcc gtg acg atg tcc ggg ggg ccg      240 
Met Ala Lys Gly Gly Tyr Tyr Pro Ser Val Thr Met Ser Gly Gly Pro 
 65                  70                  75                  80 

cag gag ttc gac ttc ggc gag atc gtc tac gat ctc acc gcg tcg cag      288 
Gln Glu Phe Asp Phe Gly Glu Ile Val Tyr Asp Leu Thr Ala Ser Gln 
                 85                  90                  95 

atg ctg tac gac tgg ggt cgg gtg acg agc aag gtc gac agc gcc agc      336 
Met Leu Tyr Asp Trp Gly Arg Val Thr Ser Lys Val Asp Ser Ala Ser 
            100                 105                 110 

gcg acc cag cgc aag ctg tcc gag gcg gtg ctg gtg gcg cgc gac gat      384 
Ala Thr Gln Arg Lys Leu Ser Glu Ala Val Leu Val Ala Arg Asp Asp 
        115                 120                 125 

gcg gcg ctg gat atc gtc gag acc tac ctc gat gtg ctt gcc tcg gag      432 
Ala Ala Leu Asp Ile Val Glu Thr Tyr Leu Asp Val Leu Ala Ser Glu 
    130                 135                 140 

cgc cgg gtg gag gcg gtg cgc gaa cac atc cag cgc ctc gac ggc atc      480 
Arg Arg Val Glu Ala Val Arg Glu His Ile Gln Arg Leu Asp Gly Ile 
145                 150                 155                 160 

cgc gag atg acc cag gcg cgc ggc ggc gac ggc tac gcc gac cgc agc      528 
Arg Glu Met Thr Gln Ala Arg Gly Gly Asp Gly Tyr Ala Asp Arg Ser 
                165                 170                 175 

gag ctg gat cgc gcc aat ctg gaa ctg tcg cgg gcc cag gag cag ttg      576 
Glu Leu Asp Arg Ala Asn Leu Glu Leu Ser Arg Ala Gln Glu Gln Leu 
            180                 185                 190 

tcg ctg gag aag ggc aac ctg cag gac gcg cgc aac cag tac gcg atc      624 
Ser Leu Glu Lys Gly Asn Leu Gln Asp Ala Arg Asn Gln Tyr Ala Ile 
        195                 200                 205 

ctg gtc ggc cag gag ccc gcc gac ctg gtg gag ccc gag ccg atg tcg      672 
Leu Val Gly Gln Glu Pro Ala Asp Leu Val Glu Pro Glu Pro Met Ser 
    210                 215                 220 

ctg caa cgc tac ctg gcg gcc agc gat atg gcg cgg gtg atc cgc gaa      720 
Leu Gln Arg Tyr Leu Ala Ala Ser Asp Met Ala Arg Val Ile Arg Glu 
225                 230                 235                 240 

tcg cct ttg cag cgc aag gcc ctg gag gac gcc aat gtc gcc gag gcc      768 
Ser Pro Leu Gln Arg Lys Ala Leu Glu Asp Ala Asn Val Ala Glu Ala 
                245                 250                 255 

gag gtc cgc gag gcc aag gcg tcg ctg ctg ccg caa ctg aac ctg gag      816 
Glu Val Arg Glu Ala Lys Ala Ser Leu Leu Pro Gln Leu Asn Leu Glu 
            260                 265                 270 

gcc agc gcg ctg cgc cgg gag atc ggc ggg cat ccg gaa agc gac tcg      864 
Ala Ser Ala Leu Arg Arg Glu Ile Gly Gly His Pro Glu Ser Asp Ser 
        275                 280                 285 

gtg gta tcc ctg cgc ttc cgc atg gac acc ttc cag ggg ctt tcc aac      912 
Val Val Ser Leu Arg Phe Arg Met Asp Thr Phe Gln Gly Leu Ser Asn 
    290                 295                 300 

ttc cgc cgg ccg acc gcc gcg cag cag cgc ctg gag tcg gcg aaa tgg      960 
Phe Arg Arg Pro Thr Ala Ala Gln Gln Arg Leu Glu Ser Ala Lys Trp 
305                 310                 315                 320 

agc gcc gac gcg atg cag cgc gac atc cgc cgg caa ctg cag aac ctc     1008 
Ser Ala Asp Ala Met Gln Arg Asp Ile Arg Arg Gln Leu Gln Asn Leu 
                325                 330                 335 

ttc gac aac ggc gac acg ctg cgc tgg cgg gaa cag tcg ctg acc cag     1056 
Phe Asp Asn Gly Asp Thr Leu Arg Trp Arg Glu Gln Ser Leu Thr Gln 
            340                 345                 350 

cag gtg acc gag tcg gag cag gtc ggc gag ttg tat cgc gaa cag ttc     1104 
Gln Val Thr Glu Ser Glu Gln Val Gly Glu Leu Tyr Arg Glu Gln Phe 
        355                 360                 365 

gag gtt ggc cgg cgc gac gtg atc gac ctg ctc aac gtg cag cgc gag     1152 
Glu Val Gly Arg Arg Asp Val Ile Asp Leu Leu Asn Val Gln Arg Glu 
    370                 375                 380 

cgg ttc gag gca gag cgg caa ctg atc aac ctg cgg atc gaa cgc aag     1200 
Arg Phe Glu Ala Glu Arg Gln Leu Ile Asn Leu Arg Ile Glu Arg Lys 
385                 390                 395                 400 

cgc atc gag tat cgg gcg gcc gcg caa gtc ggc ctg ttg ggt ccg cta     1248 
Arg Ile Glu Tyr Arg Ala Ala Ala Gln Val Gly Leu Leu Gly Pro Leu 
                405                 410                 415 

ttg gag aac cgg ctg aat cat gga agc tga                             1278 
Leu Glu Asn Arg Leu Asn His Gly Ser 
            420                 425 

 
           
             6  
             425  
             PRT  
             Pseudomonas aeruginosa  
           
            6 

Met Arg Gly Arg Arg Gln Tyr Ala Arg Lys Gly Arg Arg His Gly Lys 
 1               5                  10                  15 

Gly Ala Ile Trp Leu Leu Ser Leu Gly Leu Pro Met Phe Ala Ser Ala 
            20                  25                  30 

Met Pro Leu Asp Gln Ala Val Arg Ala Gly Leu Ala Ile His Pro Glu 
        35                  40                  45 

Val Arg Ser Ala Met Ala Glu Ala Asp Arg Ala Gly Thr Glu Val Glu 
    50                  55                  60 

Met Ala Lys Gly Gly Tyr Tyr Pro Ser Val Thr Met Ser Gly Gly Pro 
65                  70                  75                  80 

Gln Glu Phe Asp Phe Gly Glu Ile Val Tyr Asp Leu Thr Ala Ser Gln 
                85                  90                  95 

Met Leu Tyr Asp Trp Gly Arg Val Thr Ser Lys Val Asp Ser Ala Ser 
            100                 105                 110 

Ala Thr Gln Arg Lys Leu Ser Glu Ala Val Leu Val Ala Arg Asp Asp 
        115                 120                 125 

Ala Ala Leu Asp Ile Val Glu Thr Tyr Leu Asp Val Leu Ala Ser Glu 
    130                 135                 140 

Arg Arg Val Glu Ala Val Arg Glu His Ile Gln Arg Leu Asp Gly Ile 
145                 150                 155                 160 

Arg Glu Met Thr Gln Ala Arg Gly Gly Asp Gly Tyr Ala Asp Arg Ser 
                165                 170                 175 

Glu Leu Asp Arg Ala Asn Leu Glu Leu Ser Arg Ala Gln Glu Gln Leu 
            180                 185                 190 

Ser Leu Glu Lys Gly Asn Leu Gln Asp Ala Arg Asn Gln Tyr Ala Ile 
        195                 200                 205 

Leu Val Gly Gln Glu Pro Ala Asp Leu Val Glu Pro Glu Pro Met Ser 
    210                 215                 220 

Leu Gln Arg Tyr Leu Ala Ala Ser Asp Met Ala Arg Val Ile Arg Glu 
225                 230                 235                 240 

Ser Pro Leu Gln Arg Lys Ala Leu Glu Asp Ala Asn Val Ala Glu Ala 
                245                 250                 255 

Glu Val Arg Glu Ala Lys Ala Ser Leu Leu Pro Gln Leu Asn Leu Glu 
            260                 265                 270 

Ala Ser Ala Leu Arg Arg Glu Ile Gly Gly His Pro Glu Ser Asp Ser 
        275                 280                 285 

Val Val Ser Leu Arg Phe Arg Met Asp Thr Phe Gln Gly Leu Ser Asn 
    290                 295                 300 

Phe Arg Arg Pro Thr Ala Ala Gln Gln Arg Leu Glu Ser Ala Lys Trp 
305                 310                 315                 320 

Ser Ala Asp Ala Met Gln Arg Asp Ile Arg Arg Gln Leu Gln Asn Leu 
                325                 330                 335 

Phe Asp Asn Gly Asp Thr Leu Arg Trp Arg Glu Gln Ser Leu Thr Gln 
            340                 345                 350 

Gln Val Thr Glu Ser Glu Gln Val Gly Glu Leu Tyr Arg Glu Gln Phe 
        355                 360                 365 

Glu Val Gly Arg Arg Asp Val Ile Asp Leu Leu Asn Val Gln Arg Glu 
    370                 375                 380 

Arg Phe Glu Ala Glu Arg Gln Leu Ile Asn Leu Arg Ile Glu Arg Lys 
385                 390                 395                 400 
Arg Ile Glu Tyr Arg Ala Ala Ala Gln Val Gly Leu Leu Gly Pro Leu 
                405                 410                 415 

Leu Glu Asn Arg Leu Asn His Gly Ser 
            420                 425 

 
           
             7  
             2172  
             DNA  
             Pseudomonas aeruginosa  
             
               CDS  
               (1)...(2169)  
             
           
            7 

atg gaa gct gag aaa acc ccg gat aac gtc gtg atc ctc aac cac gac       48 
Met Glu Ala Glu Lys Thr Pro Asp Asn Val Val Ile Leu Asn His Asp 
 1               5                   10                  15 

ccc atc gtc gac ccg ttg cgc cag ggc ttg ttg ctg ctc tgc cgg cag       96 
Pro Ile Val Asp Pro Leu Arg Gln Gly Leu Leu Leu Leu Cys Arg Gln 
             20                  25                  30 

ctt ggc cga ccg ctc ggc gac gcc gaa ctg gtg gac ggc atg ccg ctg      144 
Leu Gly Arg Pro Leu Gly Asp Ala Glu Leu Val Asp Gly Met Pro Leu 
         35                  40                  45 

gag cac ggt cgc ctg ccg ttg cac ctg gtg gcc cgc gcg ttg cgc cgc      192 
Glu His Gly Arg Leu Pro Leu His Leu Val Ala Arg Ala Leu Arg Arg 
     50                  55                  60 

gcc gac atc acc gcc cag gtc acc cgc cag ccg ttg cgc cgg atc gat      240 
Ala Asp Ile Thr Ala Gln Val Thr Arg Gln Pro Leu Arg Arg Ile Asp 
 65                  70                  75                  80 

cgc tac ctg ctg ccg gcc ctg ctg ctg ctc gac gac ggc cgc gcc ctg      288 
Arg Tyr Leu Leu Pro Ala Leu Leu Leu Leu Asp Asp Gly Arg Ala Leu 
                 85                  90                  95 

gtg ctg gtg ggc aac gac ggc gag cac gcc gag gtg ctg gta ccg cag      336 
Val Leu Val Gly Asn Asp Gly Glu His Ala Glu Val Leu Val Pro Gln 
            100                 105                 110 

agc gac ggc gga agc cag agg atg ccg ctg gcc gag ctg gaa gcg ctg      384 
Ser Asp Gly Gly Ser Gln Arg Met Pro Leu Ala Glu Leu Glu Ala Leu 
        115                 120                 125 

tac agc ggc acg gcg gtc ttc gcc aag tgc cgc tac cgc ccg gac ggg      432 
Tyr Ser Gly Thr Ala Val Phe Ala Lys Cys Arg Tyr Arg Pro Asp Gly 
    130                 135                 140 

cgg gtc ggc gac tac gcc agc gcc ttg ccc gaa cac tgg ttc ttc ggc      480 
Arg Val Gly Asp Tyr Ala Ser Ala Leu Pro Glu His Trp Phe Phe Gly 
145                 150                 155                 160 

ccg ctc aag cgg ctc tgg cgt tcc tac gcc gag gtc acc gcc gcg gcg      528 
Pro Leu Lys Arg Leu Trp Arg Ser Tyr Ala Glu Val Thr Ala Ala Ala 
                165                 170                 175 

ttg gtg gcc aac gtc ctg gcg gtc gcc tcg gca ctg ttc gcc atg cag      576 
Leu Val Ala Asn Val Leu Ala Val Ala Ser Ala Leu Phe Ala Met Gln 
            180                 185                 190 

gtc tac gac cgc gtg gtg ccc aac gcg gcg ttc gac acc ctg tgg atc      624 
Val Tyr Asp Arg Val Val Pro Asn Ala Ala Phe Asp Thr Leu Trp Ile 
        195                 200                 205 

ctc gcc agc ggc gtg gcc ctg gcg atc gtc ctc gac ggt gtc ctg cgg      672 
Leu Ala Ser Gly Val Ala Leu Ala Ile Val Leu Asp Gly Val Leu Arg 
    210                 215                 220 

atc atg cgc ggc cac ctg ctc aac gtg ctc ggc aag cgc ctc gac ctg      720 
Ile Met Arg Gly His Leu Leu Asn Val Leu Gly Lys Arg Leu Asp Leu 
225                 230                 235                 240 

caa ctc tcg acc ctg ctg ttc tcc cgc gtg ctg agc acc cgg gtc gcc      768 
Gln Leu Ser Thr Leu Leu Phe Ser Arg Val Leu Ser Thr Arg Val Ala 
                245                 250                 255 

gcc aag ccg gcg tcg atg ggc gcc ttc agt acc cag gtg cgg gag ttc      816 
Ala Lys Pro Ala Ser Met Gly Ala Phe Ser Thr Gln Val Arg Glu Phe 
            260                 265                 270 

gag tcg gtg cgc gag ttc ttt acc tcg tcc agc gcg gcg ctg atc agc      864 
Glu Ser Val Arg Glu Phe Phe Thr Ser Ser Ser Ala Ala Leu Ile Ser 
        275                 280                 285 

gac ctg ccg ttc gtg gcg atc ttc ctg ctg atc atc gcc gtg atc ggc      912 
Asp Leu Pro Phe Val Ala Ile Phe Leu Leu Ile Ile Ala Val Ile Gly 
    290                 295                 300 

ggc cat gtg gtc tgg gtg ccg ctg gtg gcc tgc gtg ctg atg atc ctg      960 
Gly His Val Val Trp Val Pro Leu Val Ala Cys Val Leu Met Ile Leu 
305                 310                 315                 320 

ccg ggg ctg ctg acc cag cgc ctg ctc ggc cac ctg tcg cgg cag aac     1008 
Pro Gly Leu Leu Thr Gln Arg Leu Leu Gly His Leu Ser Arg Gln Asn 
                325                 330                 335 

ctg cgc gaa ggg gcg atg aag aac ggc gtg ctg ctg gaa gcc ttc gag     1056 
Leu Arg Glu Gly Ala Met Lys Asn Gly Val Leu Leu Glu Ala Phe Glu 
            340                 345                 350 

cac ctg gag acg gtc aag gcg acc cgc gcc gaa ggc cgc tgc ctg cac     1104 
His Leu Glu Thr Val Lys Ala Thr Arg Ala Glu Gly Arg Cys Leu His 
        355                 360                 365 

cag tgg gaa acc ctg acc ggc gaa ctg gcc ggt acg gcg atg aag acc     1152 
Gln Trp Glu Thr Leu Thr Gly Glu Leu Ala Gly Thr Ala Met Lys Thr 
    370                 375                 380 

cat act ctg gcc tcg acc ctg agc tac tcg gcg agc atc gtc cag cag     1200 
His Thr Leu Ala Ser Thr Leu Ser Tyr Ser Ala Ser Ile Val Gln Gln 
385                 390                 395                 400 

ctc tgc tac gtc ggc gtg gtg gtc ttc ggc gtc tat cgg atc agc gag     1248 
Leu Cys Tyr Val Gly Val Val Val Phe Gly Val Tyr Arg Ile Ser Glu 
                405                 410                 415 

ggc gcg atg acc gtc ggc ggc ctg gtg gcc tgc tcg atc ctc gcc tcg     1296 
Gly Ala Met Thr Val Gly Gly Leu Val Ala Cys Ser Ile Leu Ala Ser 
            420                 425                 430 

cgg gcc atc gca ccg ctg tcg cag gcg gcc ggc atc ctc ggt cgc tgg     1344 
Arg Ala Ile Ala Pro Leu Ser Gln Ala Ala Gly Ile Leu Gly Arg Trp 
        435                 440                 445 

cag cac acc aag gtg gcg atg gaa ggc ctc gac caa ctg atg agc gcc     1392 
Gln His Thr Lys Val Ala Met Glu Gly Leu Asp Gln Leu Met Ser Ala 
    450                 455                 460 

gag cag gag cga ccc cag ggc aag cgc ttc gtg cac aag gag cgc ctg     1440 
Glu Gln Glu Arg Pro Gln Gly Lys Arg Phe Val His Lys Glu Arg Leu 
465                 470                 475                 480 

cag gga cat tac cgc ctg gag ggc gtg cgc ctg gcc cac ggc gac agc     1488 
Gln Gly His Tyr Arg Leu Glu Gly Val Arg Leu Ala His Gly Asp Ser 
                485                 490                 495 

ccg ccg gtg gtc gac gtg cag gcc ctg aac atc cgc gcc ggc gag cgg     1536 
Pro Pro Val Val Asp Val Gln Ala Leu Asn Ile Arg Ala Gly Glu Arg 
            500                 505                 510 

gtg gcg ctg ctc ggc ggc aac ggc gcc ggc aag tcg acc ctg ctg cgc     1584 
Val Ala Leu Leu Gly Gly Asn Gly Ala Gly Lys Ser Thr Leu Leu Arg 
        515                 520                 525 

ctg ctc agc ggc ctg ctc gac gcg cag gcg gga cgc ctg ctg ctg gac     1632 
Leu Leu Ser Gly Leu Leu Asp Ala Gln Ala Gly Arg Leu Leu Leu Asp 
    530                 535                 540 

gac gtc agc ctg acc cag atc gac ccg gcc gac cgc cag cgc ggt atc     1680 
Asp Val Ser Leu Thr Gln Ile Asp Pro Ala Asp Arg Gln Arg Gly Ile 
545                 550                 555                 560 

ggc tac ctg ccg cag gac gtg gcg ctg ttc cat ggc agc ctg cgc gac     1728 
Gly Tyr Leu Pro Gln Asp Val Ala Leu Phe His Gly Ser Leu Arg Asp 
                565                 570                 575 

aac ctc aac ctg gag aac gcc gcg ctg ggc gac gag gaa ctg ctg gag     1776 
Asn Leu Asn Leu Glu Asn Ala Ala Leu Gly Asp Glu Glu Leu Leu Glu 
            580                 585                 590 

acc ctc gac ggg gtc ggc ctg ggc gcc ttc gtc cgc ggc cac ccg ctg     1824 
Thr Leu Asp Gly Val Gly Leu Gly Ala Phe Val Arg Gly His Pro Leu 
        595                 600                 605 

ggg ctg gac atg ccg atc cag ggc aac gcc agc ctg tcc ggc ggc caa     1872 
Gly Leu Asp Met Pro Ile Gln Gly Asn Ala Ser Leu Ser Gly Gly Gln 
    610                 615                 620 

cgc cag gcc gtc ggg ctg gcc cgg gtg ctg cta cag gac cct ccg atc     1920 
Arg Gln Ala Val Gly Leu Ala Arg Val Leu Leu Gln Asp Pro Pro Ile 
625                 630                 635                 640 

ctg ctg ctc gac gag ccg acc gcg gcc ttc gac cag ggc agc gag aaa     1968 
Leu Leu Leu Asp Glu Pro Thr Ala Ala Phe Asp Gln Gly Ser Glu Lys 
                645                 650                 655 

cag gtc atc gac tac ctg cag caa tgg ttg ggc aag cgc acc ctg gtc     2016 
Gln Val Ile Asp Tyr Leu Gln Gln Trp Leu Gly Lys Arg Thr Leu Val 
            660                 665                 670 

atc acc acc cac aag aaa agc atg ctc gcc ctg gtc gag cgt gcg gtg     2064 
Ile Thr Thr His Lys Lys Ser Met Leu Ala Leu Val Glu Arg Ala Val 
        675                 680                 685 

gtc ctg cgc cag ggc agg gtg atc atg gac ggc ccg ctg gag cag gtg     2112 
Val Leu Arg Gln Gly Arg Val Ile Met Asp Gly Pro Leu Glu Gln Val 
    690                 695                 700 

gtg cag ggc aac cag gta cag gca ccg cag gcc gcc gaa gga ggc aac     2160 
Val Gln Gly Asn Gln Val Gln Ala Pro Gln Ala Ala Glu Gly Gly Asn 
705                 710                 715                 720 

cat gga ctc tga                                                     2172 
His Gly Leu 

 
           
             8  
             723  
             PRT  
             Pseudomonas aeruginosa  
           
            8 

Met Glu Ala Glu Lys Thr Pro Asp Asn Val Val Ile Leu Asn His Asp 
 1               5                  10                  15 

Pro Ile Val Asp Pro Leu Arg Gln Gly Leu Leu Leu Leu Cys Arg Gln 
            20                  25                  30 

Leu Gly Arg Pro Leu Gly Asp Ala Glu Leu Val Asp Gly Met Pro Leu 
        35                  40                  45 

Glu His Gly Arg Leu Pro Leu His Leu Val Ala Arg Ala Leu Arg Arg 
    50                  55                  60 

Ala Asp Ile Thr Ala Gln Val Thr Arg Gln Pro Leu Arg Arg Ile Asp 
65                  70                  75                  80 

Arg Tyr Leu Leu Pro Ala Leu Leu Leu Leu Asp Asp Gly Arg Ala Leu 
                85                  90                  95 

Val Leu Val Gly Asn Asp Gly Glu His Ala Glu Val Leu Val Pro Gln 
            100                 105                 110 

Ser Asp Gly Gly Ser Gln Arg Met Pro Leu Ala Glu Leu Glu Ala Leu 
        115                 120                 125 

Tyr Ser Gly Thr Ala Val Phe Ala Lys Cys Arg Tyr Arg Pro Asp Gly 
    130                 135                 140 

Arg Val Gly Asp Tyr Ala Ser Ala Leu Pro Glu His Trp Phe Phe Gly 
145                 150                 155                 160 

Pro Leu Lys Arg Leu Trp Arg Ser Tyr Ala Glu Val Thr Ala Ala Ala 
                165                 170                 175 

Leu Val Ala Asn Val Leu Ala Val Ala Ser Ala Leu Phe Ala Met Gln 
            180                 185                 190 

Val Tyr Asp Arg Val Val Pro Asn Ala Ala Phe Asp Thr Leu Trp Ile 
        195                 200                 205 

Leu Ala Ser Gly Val Ala Leu Ala Ile Val Leu Asp Gly Val Leu Arg 
    210                 215                 220 

Ile Met Arg Gly His Leu Leu Asn Val Leu Gly Lys Arg Leu Asp Leu 
225                 230                 235                 240 

Gln Leu Ser Thr Leu Leu Phe Ser Arg Val Leu Ser Thr Arg Val Ala 
                245                 250                 255 

Ala Lys Pro Ala Ser Met Gly Ala Phe Ser Thr Gln Val Arg Glu Phe 
            260                 265                 270 

Glu Ser Val Arg Glu Phe Phe Thr Ser Ser Ser Ala Ala Leu Ile Ser 
        275                 280                 285 

Asp Leu Pro Phe Val Ala Ile Phe Leu Leu Ile Ile Ala Val Ile Gly 
    290                 295                 300 

Gly His Val Val Trp Val Pro Leu Val Ala Cys Val Leu Met Ile Leu 
305                 310                 315                 320 

Pro Gly Leu Leu Thr Gln Arg Leu Leu Gly His Leu Ser Arg Gln Asn 
                325                 330                 335 

Leu Arg Glu Gly Ala Met Lys Asn Gly Val Leu Leu Glu Ala Phe Glu 
            340                 345                 350 

His Leu Glu Thr Val Lys Ala Thr Arg Ala Glu Gly Arg Cys Leu His 
        355                 360                 365 

Gln Trp Glu Thr Leu Thr Gly Glu Leu Ala Gly Thr Ala Met Lys Thr 
    370                 375                 380 

His Thr Leu Ala Ser Thr Leu Ser Tyr Ser Ala Ser Ile Val Gln Gln 
385                 390                 395                 400 

Leu Cys Tyr Val Gly Val Val Val Phe Gly Val Tyr Arg Ile Ser Glu 
                405                 410                 415 

Gly Ala Met Thr Val Gly Gly Leu Val Ala Cys Ser Ile Leu Ala Ser 
            420                 425                 430 

Arg Ala Ile Ala Pro Leu Ser Gln Ala Ala Gly Ile Leu Gly Arg Trp 
        435                 440                 445 

Gln His Thr Lys Val Ala Met Glu Gly Leu Asp Gln Leu Met Ser Ala 
    450                 455                 460 

Glu Gln Glu Arg Pro Gln Gly Lys Arg Phe Val His Lys Glu Arg Leu 
465                 470                 475                 480 

Gln Gly His Tyr Arg Leu Glu Gly Val Arg Leu Ala His Gly Asp Ser 
                485                 490                 495 

Pro Pro Val Val Asp Val Gln Ala Leu Asn Ile Arg Ala Gly Glu Arg 
            500                 505                 510 

Val Ala Leu Leu Gly Gly Asn Gly Ala Gly Lys Ser Thr Leu Leu Arg 
        515                 520                 525 

Leu Leu Ser Gly Leu Leu Asp Ala Gln Ala Gly Arg Leu Leu Leu Asp 
    530                 535                 540 

Asp Val Ser Leu Thr Gln Ile Asp Pro Ala Asp Arg Gln Arg Gly Ile 
545                 550                 555                 560 

Gly Tyr Leu Pro Gln Asp Val Ala Leu Phe His Gly Ser Leu Arg Asp 
                565                 570                 575 

Asn Leu Asn Leu Glu Asn Ala Ala Leu Gly Asp Glu Glu Leu Leu Glu 
            580                 585                 590 

Thr Leu Asp Gly Val Gly Leu Gly Ala Phe Val Arg Gly His Pro Leu 
        595                 600                 605 

Gly Leu Asp Met Pro Ile Gln Gly Asn Ala Ser Leu Ser Gly Gly Gln 
    610                 615                 620 

Arg Gln Ala Val Gly Leu Ala Arg Val Leu Leu Gln Asp Pro Pro Ile 
625                 630                 635                 640 

Leu Leu Leu Asp Glu Pro Thr Ala Ala Phe Asp Gln Gly Ser Glu Lys 
                645                 650                 655 

Gln Val Ile Asp Tyr Leu Gln Gln Trp Leu Gly Lys Arg Thr Leu Val 
            660                 665                 670 

Ile Thr Thr His Lys Lys Ser Met Leu Ala Leu Val Glu Arg Ala Val 
        675                 680                 685 

Val Leu Arg Gln Gly Arg Val Ile Met Asp Gly Pro Leu Glu Gln Val 
    690                 695                 700 

Val Gln Gly Asn Gln Val Gln Ala Pro Gln Ala Ala Glu Gly Gly Asn 
705                 710                 715                 720 

His Gly Leu 

 
           
             9  
             1188  
             DNA  
             Pseudomonas aeruginosa  
             
               CDS  
               (1)...(1185)  
             
           
            9 

atg gac tct gac cgc gac gcc gcc gcc ctg cgc cgg caa ctg gcc gac       48 
Met Asp Ser Asp Arg Asp Ala Ala Ala Leu Arg Arg Gln Leu Ala Asp 
 1               5                   10                  15 

ccg ttg ctg gcg gct acc cac ccg gtc tac cgg ccg ctg ctc tgg acc       96 
Pro Leu Leu Ala Ala Thr His Pro Val Tyr Arg Pro Leu Leu Trp Thr 
             20                  25                  30 

ctg ctc ggt tgc gtg ctg ctg ttc atc ggc tgg gcg gcc tgg gcg caa      144 
Leu Leu Gly Cys Val Leu Leu Phe Ile Gly Trp Ala Ala Trp Ala Gln 
         35                  40                  45 

ctg gac gag gtg acc cgc ggc gac ggt cgg gtc gtg ccg ttc agc cgc      192 
Leu Asp Glu Val Thr Arg Gly Asp Gly Arg Val Val Pro Phe Ser Arg 
     50                  55                  60 

atc cag aag atc cag agc ctg gag ggc ggc atc ctc gac cgc ctg ctg      240 
Ile Gln Lys Ile Gln Ser Leu Glu Gly Gly Ile Leu Asp Arg Leu Leu 
 65                  70                  75                  80 

gtg aag gag ggc gac ctg gtg gaa gtc ggc cag ccg ctg gtg cgc ctc      288 
Val Lys Glu Gly Asp Leu Val Glu Val Gly Gln Pro Leu Val Arg Leu 
                 85                  90                  95 

gac gag acg cgc ttc ctc acc aac ttc cag gag tcg gcg aac cag gcc      336 
Asp Glu Thr Arg Phe Leu Thr Asn Phe Gln Glu Ser Ala Asn Gln Ala 
            100                 105                 110 

agc gtg ctg cgc gcg gcc att gcc cgg ctc gac gcc gag gtg cta ggc      384 
Ser Val Leu Arg Ala Ala Ile Ala Arg Leu Asp Ala Glu Val Leu Gly 
        115                 120                 125 

aag aag agc atc gag ttc ccg ccg gac gtc gat ccc gag ggg ccg ctg      432 
Lys Lys Ser Ile Glu Phe Pro Pro Asp Val Asp Pro Glu Gly Pro Leu 
    130                 135                 140 

gcg cgt tcc gaa cgc gag ctg ttc aag tcg cgc cgc gac aaa ctg gtg      480 
Ala Arg Ser Glu Arg Glu Leu Phe Lys Ser Arg Arg Asp Lys Leu Val 
145                 150                 155                 160 

gag ggc acc cag gcg atc cag cgg cag atc cac ctg gcg cag agc cag      528 
Glu Gly Thr Gln Ala Ile Gln Arg Gln Ile His Leu Ala Gln Ser Gln 
                165                 170                 175 

ctc gac ctg gtt cgc ccg ctg gtg gcc aag cgt gcg gtg agc cag atg      576 
Leu Asp Leu Val Arg Pro Leu Val Ala Lys Arg Ala Val Ser Gln Met 
            180                 185                 190 

gag gcg ctc aag ctg agc cag gac atc gcc acc ctc agc ggc aag ctg      624 
Glu Ala Leu Lys Leu Ser Gln Asp Ile Ala Thr Leu Ser Gly Lys Leu 
        195                 200                 205 

acc gag ctg aaa agc acc tat ttc cag gat gcc tat acc gag cgc gcc      672 
Thr Glu Leu Lys Ser Thr Tyr Phe Gln Asp Ala Tyr Thr Glu Arg Ala 
    210                 215                 220 

cag cgc aag gcc gat ctc agc gcc ctg gaa ccg atc gtc cag cag cgc      720 
Gln Arg Lys Ala Asp Leu Ser Ala Leu Glu Pro Ile Val Gln Gln Arg 
225                 230                 235                 240 

cag gac cag ttg cgc cgc acc gag atc ctg tcg cca gtg cgc ggg cgg      768 
Gln Asp Gln Leu Arg Arg Thr Glu Ile Leu Ser Pro Val Arg Gly Arg 
                245                 250                 255 

gtg aac acc gtg ctg atc aac acc cgc ggc ggg gtg atc cag ccc ggc      816 
Val Asn Thr Val Leu Ile Asn Thr Arg Gly Gly Val Ile Gln Pro Gly 
            260                 265                 270 

gag ccg atc atg gaa gtg atc ccg gta gag gag cgt ctg ctg gtg gag      864 
Glu Pro Ile Met Glu Val Ile Pro Val Glu Glu Arg Leu Leu Val Glu 
        275                 280                 285 

gcg aag atc aag ccg cgc gac gtg gcc ttc ctg gtt ccc ggc atg ccg      912 
Ala Lys Ile Lys Pro Arg Asp Val Ala Phe Leu Val Pro Gly Met Pro 
    290                 295                 300 

gcc aag gtg aag atc acc gcc tac gac tac acc atc tac ggc gac ctc      960 
Ala Lys Val Lys Ile Thr Ala Tyr Asp Tyr Thr Ile Tyr Gly Asp Leu 
305                 310                 315                 320 

aag ggc acc ctg gag cag atc agt gcc gac acc atc gag gag gac acc     1008 
Lys Gly Thr Leu Glu Gln Ile Ser Ala Asp Thr Ile Glu Glu Asp Thr 
                325                 330                 335 

ccg cat ggc aag gag tcc tac tac cag gtg ctg atc aag acc gat ggc     1056 
Pro His Gly Lys Glu Ser Tyr Tyr Gln Val Leu Ile Lys Thr Asp Gly 
            340                 345                 350 

agc cag ttg aag cgc ggc gag gag gta ttg ccg atc att ccg ggg atg     1104 
Ser Gln Leu Lys Arg Gly Glu Glu Val Leu Pro Ile Ile Pro Gly Met 
        355                 360                 365 

gtc gcc gag gtg gac atc ctc agc ggc aag cgc agc gtg ctc aac tac     1152 
Val Ala Glu Val Asp Ile Leu Ser Gly Lys Arg Ser Val Leu Asn Tyr 
    370                 375                 380 

ctg ctg cgg ccg ctg atc aag gcg cgc ctt tac tga                     1188 
Leu Leu Arg Pro Leu Ile Lys Ala Arg Leu Tyr 
385                 390                 395 

 
           
             10  
             395  
             PRT  
             Pseudomonas aeruginosa  
           
            10 

Met Asp Ser Asp Arg Asp Ala Ala Ala Leu Arg Arg Gln Leu Ala Asp 
 1               5                  10                  15 

Pro Leu Leu Ala Ala Thr His Pro Val Tyr Arg Pro Leu Leu Trp Thr 
            20                  25                  30 

Leu Leu Gly Cys Val Leu Leu Phe Ile Gly Trp Ala Ala Trp Ala Gln 
        35                  40                  45 

Leu Asp Glu Val Thr Arg Gly Asp Gly Arg Val Val Pro Phe Ser Arg 
    50                  55                  60 

Ile Gln Lys Ile Gln Ser Leu Glu Gly Gly Ile Leu Asp Arg Leu Leu 
65                  70                  75                  80 

Val Lys Glu Gly Asp Leu Val Glu Val Gly Gln Pro Leu Val Arg Leu 
                85                  90                  95 

Asp Glu Thr Arg Phe Leu Thr Asn Phe Gln Glu Ser Ala Asn Gln Ala 
            100                 105                 110 

Ser Val Leu Arg Ala Ala Ile Ala Arg Leu Asp Ala Glu Val Leu Gly 
        115                 120                 125 

Lys Lys Ser Ile Glu Phe Pro Pro Asp Val Asp Pro Glu Gly Pro Leu 
    130                 135                 140 

Ala Arg Ser Glu Arg Glu Leu Phe Lys Ser Arg Arg Asp Lys Leu Val 
145                 150                 155                 160 

Glu Gly Thr Gln Ala Ile Gln Arg Gln Ile His Leu Ala Gln Ser Gln 
                165                 170                 175 

Leu Asp Leu Val Arg Pro Leu Val Ala Lys Arg Ala Val Ser Gln Met 
            180                 185                 190 

Glu Ala Leu Lys Leu Ser Gln Asp Ile Ala Thr Leu Ser Gly Lys Leu 
        195                 200                 205 

Thr Glu Leu Lys Ser Thr Tyr Phe Gln Asp Ala Tyr Thr Glu Arg Ala 
    210                 215                 220 

Gln Arg Lys Ala Asp Leu Ser Ala Leu Glu Pro Ile Val Gln Gln Arg 
225                 230                 235                 240 

Gln Asp Gln Leu Arg Arg Thr Glu Ile Leu Ser Pro Val Arg Gly Arg 
                245                 250                 255 

Val Asn Thr Val Leu Ile Asn Thr Arg Gly Gly Val Ile Gln Pro Gly 
            260                 265                 270 

Glu Pro Ile Met Glu Val Ile Pro Val Glu Glu Arg Leu Leu Val Glu 
        275                 280                 285 

Ala Lys Ile Lys Pro Arg Asp Val Ala Phe Leu Val Pro Gly Met Pro 
    290                 295                 300 

Ala Lys Val Lys Ile Thr Ala Tyr Asp Tyr Thr Ile Tyr Gly Asp Leu 
305                 310                 315                 320 

Lys Gly Thr Leu Glu Gln Ile Ser Ala Asp Thr Ile Glu Glu Asp Thr 
                325                 330                 335 

Pro His Gly Lys Glu Ser Tyr Tyr Gln Val Leu Ile Lys Thr Asp Gly 
            340                 345                 350 

Ser Gln Leu Lys Arg Gly Glu Glu Val Leu Pro Ile Ile Pro Gly Met 
        355                 360                 365 

Val Ala Glu Val Asp Ile Leu Ser Gly Lys Arg Ser Val Leu Asn Tyr 
    370                 375                 380 

Leu Leu Arg Pro Leu Ile Lys Ala Arg Leu Tyr 
385                 390                 395 

 
           
             11  
             1257  
             DNA  
             Pseudomonas aeruginosa  
             
               CDS  
               (1)...(1254)  
             
           
            11 

atg ttt cgc cag gaa gcc ctc gac gcc cag cat gcc ggc ggc ctg ggc       48 
Met Phe Arg Gln Glu Ala Leu Asp Ala Gln His Ala Gly Gly Leu Gly 
 1               5                   10                  15 

gag atc gtg ctg atc cgc ccg gtc tcc ttc act ttt ctc acc ctg ctg       96 
Glu Ile Val Leu Ile Arg Pro Val Ser Phe Thr Phe Leu Thr Leu Leu 
             20                  25                  30 

gcc gcg gcg atg gcg ctg ctg gtg gtg ggc ttc ttc ctg ttc ggc agc      144 
Ala Ala Ala Met Ala Leu Leu Val Val Gly Phe Phe Leu Phe Gly Ser 
         35                  40                  45 

tac acc aag cgc agc acc gtc agc ggc caa ttg gtg ccc gcc agc ggc      192 
Tyr Thr Lys Arg Ser Thr Val Ser Gly Gln Leu Val Pro Ala Ser Gly 
     50                  55                  60 

cag gtc aag gtg cac gcg ccg cag gcc ggc atc gtg ctg cgc aag ttc      240 
Gln Val Lys Val His Ala Pro Gln Ala Gly Ile Val Leu Arg Lys Phe 
 65                  70                  75                  80 

gtc cag gaa ggc cag gcg gta cga cgt ggc gag cgc ctg atg gtg ctt      288 
Val Gln Glu Gly Gln Ala Val Arg Arg Gly Glu Arg Leu Met Val Leu 
                 85                  90                  95 

tcc agc gaa cgc tac ggc agc gat gcc ggg ccg gtg cag gcc ggc atc      336 
Ser Ser Glu Arg Tyr Gly Ser Asp Ala Gly Pro Val Gln Ala Gly Ile 
            100                 105                 110 

agc agg cgc ctg gaa caa cgc cgc gac tcc ctg cgc gac gaa ctg gaa      384 
Ser Arg Arg Leu Glu Gln Arg Arg Asp Ser Leu Arg Asp Glu Leu Glu 
        115                 120                 125 

aag ctt cgc cgc ctg caa gac gac gag cgc gac agc ctg acc agc aag      432 
Lys Leu Arg Arg Leu Gln Asp Asp Glu Arg Asp Ser Leu Thr Ser Lys 
    130                 135                 140 

gtc gcc agc ctg cag cgc gaa ctc acc acc ctc gcc gcc cag acc gac      480 
Val Ala Ser Leu Gln Arg Glu Leu Thr Thr Leu Ala Ala Gln Thr Asp 
145                 150                 155                 160 

agc cag caa cgc ctg ctg gcg ctg gcc agc gac gcc gcc gcg cgc tac      528 
Ser Gln Gln Arg Leu Leu Ala Leu Ala Ser Asp Ala Ala Ala Arg Tyr 
                165                 170                 175 

cag ggg ctg atg gac aag ggc tac atc tcc atg gac cag ttg cag cag      576 
Gln Gly Leu Met Asp Lys Gly Tyr Ile Ser Met Asp Gln Leu Gln Gln 
            180                 185                 190 

cgc cag gcc gag ctg ctc ggc cag cgc cag acc ctg caa ggc ctg gag      624 
Arg Gln Ala Glu Leu Leu Gly Gln Arg Gln Thr Leu Gln Gly Leu Glu 
        195                 200                 205 

cgc gaa cgc acg tcg ctg cgg cag cag ttg acc gag cgc cgc aac gaa      672 
Arg Glu Arg Thr Ser Leu Arg Gln Gln Leu Thr Glu Arg Arg Asn Glu 
    210                 215                 220 

ctc gcc ggg ctt tcc gcg cgc cag gcc aac cag ctc gcg gaa acc cgc      720 
Leu Ala Gly Leu Ser Ala Arg Gln Ala Asn Gln Leu Ala Glu Thr Arg 
225                 230                 235                 240 

cgc cag ctc agc gcg gtg gag cag gac ctg gcc gaa agc gaa gcc aag      768 
Arg Gln Leu Ser Ala Val Glu Gln Asp Leu Ala Glu Ser Glu Ala Lys 
                245                 250                 255 

cgc acc ttg ctg gtc acc gcg ccg gag agc ggc atc gcc acc gcc gtg      816 
Arg Thr Leu Leu Val Thr Ala Pro Glu Ser Gly Ile Ala Thr Ala Val 
            260                 265                 270 

ctc gcc gaa gcc ggg cag acc gtc gac agc tcg cgt ccg ctg ctg agc      864 
Leu Ala Glu Ala Gly Gln Thr Val Asp Ser Ser Arg Pro Leu Leu Ser 
        275                 280                 285 

atc gtt ccc gcc gac acc ccg ttg cag gcc gaa ctc tac gcg ccg agc      912 
Ile Val Pro Ala Asp Thr Pro Leu Gln Ala Glu Leu Tyr Ala Pro Ser 
    290                 295                 300 

aag tcc atc ggt ttc atc cgg ccg ggc gac gcg gtg ctg atc cgc tac      960 
Lys Ser Ile Gly Phe Ile Arg Pro Gly Asp Ala Val Leu Ile Arg Tyr 
305                 310                 315                 320 

cag gcc tat ccg tac cag aag ttc ggc cag tac cac ggc aag gtg cag     1008 
Gln Ala Tyr Pro Tyr Gln Lys Phe Gly Gln Tyr His Gly Lys Val Gln 
                325                 330                 335 

tcg atc tcc cgc gcc agc gtc tcc tat gcc gag ctt tcc agc atg gtc     1056 
Ser Ile Ser Arg Ala Ser Val Ser Tyr Ala Glu Leu Ser Ser Met Val 
            340                 345                 350 

ggc ggc gta ccg ggg ctc ggc cag gat ggc gag cag ctg tac cgg ctg     1104 
Gly Gly Val Pro Gly Leu Gly Gln Asp Gly Glu Gln Leu Tyr Arg Leu 
        355                 360                 365 

cgg gta acc ctc gac gac cag gcg gtg acc gcc tac ggc cag ccg cgt     1152 
Arg Val Thr Leu Asp Asp Gln Ala Val Thr Ala Tyr Gly Gln Pro Arg 
    370                 375                 380 

ccg ctg cag agc ggc atg ctg ctg gac gcc gac atc ctc cag gac acc     1200 
Pro Leu Gln Ser Gly Met Leu Leu Asp Ala Asp Ile Leu Gln Asp Thr 
385                 390                 395                 400 

cgg cgc ctc tac gaa tgg gtg ctg gaa ccg ctc tac agc ctg acc ggc     1248 
Arg Arg Leu Tyr Glu Trp Val Leu Glu Pro Leu Tyr Ser Leu Thr Gly 
                405                 410                 415 

aaa ctc tag                                                         1257 
Lys Leu 

 
           
             12  
             418  
             PRT  
             Pseudomonas aeruginosa  
           
            12 

Met Phe Arg Gln Glu Ala Leu Asp Ala Gln His Ala Gly Gly Leu Gly 
 1               5                  10                  15 

Glu Ile Val Leu Ile Arg Pro Val Ser Phe Thr Phe Leu Thr Leu Leu 
            20                  25                  30 

Ala Ala Ala Met Ala Leu Leu Val Val Gly Phe Phe Leu Phe Gly Ser 
        35                  40                  45 

Tyr Thr Lys Arg Ser Thr Val Ser Gly Gln Leu Val Pro Ala Ser Gly 
    50                  55                  60 

Gln Val Lys Val His Ala Pro Gln Ala Gly Ile Val Leu Arg Lys Phe 
65                  70                  75                  80 

Val Gln Glu Gly Gln Ala Val Arg Arg Gly Glu Arg Leu Met Val Leu 
                85                  90                  95 

Ser Ser Glu Arg Tyr Gly Ser Asp Ala Gly Pro Val Gln Ala Gly Ile 
            100                 105                 110 

Ser Arg Arg Leu Glu Gln Arg Arg Asp Ser Leu Arg Asp Glu Leu Glu 
        115                 120                 125 

Lys Leu Arg Arg Leu Gln Asp Asp Glu Arg Asp Ser Leu Thr Ser Lys 
    130                 135                 140 

Val Ala Ser Leu Gln Arg Glu Leu Thr Thr Leu Ala Ala Gln Thr Asp 
145                 150                 155                 160 

Ser Gln Gln Arg Leu Leu Ala Leu Ala Ser Asp Ala Ala Ala Arg Tyr 
                165                 170                 175 

Gln Gly Leu Met Asp Lys Gly Tyr Ile Ser Met Asp Gln Leu Gln Gln 
            180                 185                 190 

Arg Gln Ala Glu Leu Leu Gly Gln Arg Gln Thr Leu Gln Gly Leu Glu 
        195                 200                 205 

Arg Glu Arg Thr Ser Leu Arg Gln Gln Leu Thr Glu Arg Arg Asn Glu 
    210                 215                 220 

Leu Ala Gly Leu Ser Ala Arg Gln Ala Asn Gln Leu Ala Glu Thr Arg 
225                 230                 235                 240 

Arg Gln Leu Ser Ala Val Glu Gln Asp Leu Ala Glu Ser Glu Ala Lys 
                245                 250                 255 

Arg Thr Leu Leu Val Thr Ala Pro Glu Ser Gly Ile Ala Thr Ala Val 
            260                 265                 270 

Leu Ala Glu Ala Gly Gln Thr Val Asp Ser Ser Arg Pro Leu Leu Ser 
        275                 280                 285 

Ile Val Pro Ala Asp Thr Pro Leu Gln Ala Glu Leu Tyr Ala Pro Ser 
    290                 295                 300 

Lys Ser Ile Gly Phe Ile Arg Pro Gly Asp Ala Val Leu Ile Arg Tyr 
305                 310                 315                 320 

Gln Ala Tyr Pro Tyr Gln Lys Phe Gly Gln Tyr His Gly Lys Val Gln 
                325                 330                 335 

Ser Ile Ser Arg Ala Ser Val Ser Tyr Ala Glu Leu Ser Ser Met Val 
            340                 345                 350 

Gly Gly Val Pro Gly Leu Gly Gln Asp Gly Glu Gln Leu Tyr Arg Leu 
        355                 360                 365 

Arg Val Thr Leu Asp Asp Gln Ala Val Thr Ala Tyr Gly Gln Pro Arg 
    370                 375                 380 

Pro Leu Gln Ser Gly Met Leu Leu Asp Ala Asp Ile Leu Gln Asp Thr 
385                 390                 395                 400 

Arg Arg Leu Tyr Glu Trp Val Leu Glu Pro Leu Tyr Ser Leu Thr Gly 
                405                 410                 415 

Lys Leu 

 
           
             13  
             2160  
             DNA  
             Pseudomonas aeruginosa  
             
               CDS  
               (1)...(2157)  
             
           
            13 

atg gcc ttt ctc gac gct ctc gcc ctg cgc ctg ggc cgc cgc ctg ccg       48 
Met Ala Phe Leu Asp Ala Leu Ala Leu Arg Leu Gly Arg Arg Leu Pro 
 1               5                   10                  15 

ctg gtg ctg cag acc gaa gcc acc gaa tgc ggc ctg gcc tgc ctg gcg       96 
Leu Val Leu Gln Thr Glu Ala Thr Glu Cys Gly Leu Ala Cys Leu Ala 
             20                  25                  30 

atg atc gcc ggc tac cac ggc cac cat acc ggc ctg atg gaa ctg cgc      144 
Met Ile Ala Gly Tyr His Gly His His Thr Gly Leu Met Glu Leu Arg 
         35                  40                  45 

cgg cgc ttc tcc gta tcg ctc aag ggc atc tcc ctc aag caa ctg atc      192 
Arg Arg Phe Ser Val Ser Leu Lys Gly Ile Ser Leu Lys Gln Leu Ile 
     50                  55                  60 

cag acc gcc cac cgc ctc ggc ctg ggt acc cgc gcg gtg aag ctc gac      240 
Gln Thr Ala His Arg Leu Gly Leu Gly Thr Arg Ala Val Lys Leu Asp 
 65                  70                  75                  80 

ctc ggc gac ctc ggc aag ctc aag ctg ccc tgc gtg ctg cac tgg aac      288 
Leu Gly Asp Leu Gly Lys Leu Lys Leu Pro Cys Val Leu His Trp Asn 
                 85                  90                  95 

ttc aac cac ttc gtc gtg ctc aag gcg gtc gac ggg cgc ggc gcg gtg      336 
Phe Asn His Phe Val Val Leu Lys Ala Val Asp Gly Arg Gly Ala Val 
            100                 105                 110 

ctc cac gac ccc gcc cac ggc cag cgc cgg ctg ggc ctg gag gaa gtc      384 
Leu His Asp Pro Ala His Gly Gln Arg Arg Leu Gly Leu Glu Glu Val 
        115                 120                 125 

tcg cgg agc ttc acc ggg gta gcc ctg gaa ctc tgg ccg gag agc ggc      432 
Ser Arg Ser Phe Thr Gly Val Ala Leu Glu Leu Trp Pro Glu Ser Gly 
    130                 135                 140 

ttc gag aaa cag gag gcg ccg ccg cgg atc aag ctg ctg ggc atg ctc      480 
Phe Glu Lys Gln Glu Ala Pro Pro Arg Ile Lys Leu Leu Gly Met Leu 
145                 150                 155                 160 

ggc aag gtc acc ggg ctg tac cgc tcg ctg gcc cag gtg ctg ctg ctc      528 
Gly Lys Val Thr Gly Leu Tyr Arg Ser Leu Ala Gln Val Leu Leu Leu 
                165                 170                 175 

gcc ggc gcg ctg gaa gtg ttc tcg ctg atc agt ccg ttc ttc ctg caa      576 
Ala Gly Ala Leu Glu Val Phe Ser Leu Ile Ser Pro Phe Phe Leu Gln 
            180                 185                 190 

tgg acc atc gac aac gtc atc gtc agc gaa gac cgt gac ctg ctc agc      624 
Trp Thr Ile Asp Asn Val Ile Val Ser Glu Asp Arg Asp Leu Leu Ser 
        195                 200                 205 

acc ctg gcc atc ggc ttc ggc ctg ttg ctg ctg atg cag cag gcg gtc      672 
Thr Leu Ala Ile Gly Phe Gly Leu Leu Leu Leu Met Gln Gln Ala Val 
    210                 215                 220 

agc ggg gtg cgc gcc tgg gtg atg atg cac atg agc acc ctg ctc ggc      720 
Ser Gly Val Arg Ala Trp Val Met Met His Met Ser Thr Leu Leu Gly 
225                 230                 235                 240 

gtg cag tgg cag gcc aac gtc ttc agc cac ctg ctg cgg ctg ccc gcg      768 
Val Gln Trp Gln Ala Asn Val Phe Ser His Leu Leu Arg Leu Pro Ala 
                245                 250                 255 

cag tat ttc gag aag cgc cac ctg ggc gac gtg gtg tcg cgc ttc ggc      816 
Gln Tyr Phe Glu Lys Arg His Leu Gly Asp Val Val Ser Arg Phe Gly 
            260                 265                 270 

gcg gtg aac agc atc cag cag acc ctc acc gcg gcc ttc ctc tcg gcg      864 
Ala Val Asn Ser Ile Gln Gln Thr Leu Thr Ala Ala Phe Leu Ser Ala 
        275                 280                 285 

gtg ctg gac ggc ctg atg acc gtc gcc acc ctc ggc atg atg ctg ctc      912 
Val Leu Asp Gly Leu Met Thr Val Ala Thr Leu Gly Met Met Leu Leu 
    290                 295                 300 

tac agt ccg cca ctg gcg gcc atc gcc atc gcc gcc atg agc ctc tac      960 
Tyr Ser Pro Pro Leu Ala Ala Ile Ala Ile Ala Ala Met Ser Leu Tyr 
305                 310                 315                 320 

gcc ctc ggc cgc tgg atc tgg tac cgg ccg ttg cgc aac gcc acc gag     1008 
Ala Leu Gly Arg Trp Ile Trp Tyr Arg Pro Leu Arg Asn Ala Thr Glu 
                325                 330                 335 

gag cag atc gtc cac gcc gcg cgc cag cag agc cac ttc ctc gag acg     1056 
Glu Gln Ile Val His Ala Ala Arg Gln Gln Ser His Phe Leu Glu Thr 
            340                 345                 350 

gtg cgc ggc atc cgc ccg ctg aag ctg ttc cag cgc cag gac gag cgc     1104 
Val Arg Gly Ile Arg Pro Leu Lys Leu Phe Gln Arg Gln Asp Glu Arg 
        355                 360                 365 

cgc tcg gta tgg ctc ggc ctg ctg gtg gaa cag atc aac gcc ggc ctg     1152 
Arg Ser Val Trp Leu Gly Leu Leu Val Glu Gln Ile Asn Ala Gly Leu 
    370                 375                 380 

cgt acg cag aag ctg caa ctg ttc tac cag cag ctc aac ggc ctg ctg     1200 
Arg Thr Gln Lys Leu Gln Leu Phe Tyr Gln Gln Leu Asn Gly Leu Leu 
385                 390                 395                 400 

ttc ggc gtg gag aac ctg ctg gtg atc tgg ctc ggc gcg acc atg gtg     1248 
Phe Gly Val Glu Asn Leu Leu Val Ile Trp Leu Gly Ala Thr Met Val 
                405                 410                 415 

atg gac ggc cag ttc agc gtc ggc atc ctg atg gcc ttc aac gcc tac     1296 
Met Asp Gly Gln Phe Ser Val Gly Ile Leu Met Ala Phe Asn Ala Tyr 
            420                 425                 430 

aag tcg cag ttc gac agc cgc gtc ggc agc ctg atc gac aag ttc ttc     1344 
Lys Ser Gln Phe Asp Ser Arg Val Gly Ser Leu Ile Asp Lys Phe Phe 
        435                 440                 445 

gag ctg cgc atg ctc cag ttg cag ggc gag cgc ctg gcc gac atc gtg     1392 
Glu Leu Arg Met Leu Gln Leu Gln Gly Glu Arg Leu Ala Asp Ile Val 
    450                 455                 460 

ctc cag gcc ccg gag gtc agc cac ggc gac atc ctc ccg gag aac ctc     1440 
Leu Gln Ala Pro Glu Val Ser His Gly Asp Ile Leu Pro Glu Asn Leu 
465                 470                 475                 480 

cgc gag cgc gag gcg agc atc gag atc cag ggc ctg cgc tac cgc tac     1488 
Arg Glu Arg Glu Ala Ser Ile Glu Ile Gln Gly Leu Arg Tyr Arg Tyr 
                485                 490                 495 

gcg gaa cag gag ccc tgg gtc ctc gac ggc ctc gac ctg cgc atc gcc     1536 
Ala Glu Gln Glu Pro Trp Val Leu Asp Gly Leu Asp Leu Arg Ile Ala 
            500                 505                 510 

ggc ggc gag tcg gtg gcc atc gtc ggc ccc tcg ggc tgc ggc aag agc     1584 
Gly Gly Glu Ser Val Ala Ile Val Gly Pro Ser Gly Cys Gly Lys Ser 
        515                 520                 525 

acc ctg ttc aac gtc ctg ctg ggc atc ctc ccg cca gtg gag gga cag     1632 
Thr Leu Phe Asn Val Leu Leu Gly Ile Leu Pro Pro Val Glu Gly Gln 
    530                 535                 540 

atc cgc atg gcc ggc ctg gac ctt gcg caa ctg ggc ctg gac ggc ctg     1680 
Ile Arg Met Ala Gly Leu Asp Leu Ala Gln Leu Gly Leu Asp Gly Leu 
545                 550                 555                 560 

cgc gaa ctg gtc ggc acg gtg ctg cag gac gac gtg ctg ttc gcc ggt     1728 
Arg Glu Leu Val Gly Thr Val Leu Gln Asp Asp Val Leu Phe Ala Gly 
                565                 570                 575 

tcg ctc agc gac aac atc agt ttc ttc gac ccg caa ccg gac atg ccc     1776 
Ser Leu Ser Asp Asn Ile Ser Phe Phe Asp Pro Gln Pro Asp Met Pro 
            580                 585                 590 

tgg ctg ctg cag tgc gcg cag atg gct gcc atc cac gat gac atc cag     1824 
Trp Leu Leu Gln Cys Ala Gln Met Ala Ala Ile His Asp Asp Ile Gln 
        595                 600                 605 

gcc atg ccg atg ggc tac aac acc ctg gtc ggc gac atg ggc acg gtg     1872 
Ala Met Pro Met Gly Tyr Asn Thr Leu Val Gly Asp Met Gly Thr Val 
    610                 615                 620 

ctc tcc ggc ggc cag aag cag cgg gtg atg ctg gcc cgg gcg ctg tac     1920 
Leu Ser Gly Gly Gln Lys Gln Arg Val Met Leu Ala Arg Ala Leu Tyr 
625                 630                 635                 640 

aag aag ccg cgc atc ctg ttc ctc gac gaa gcc acc agc cac ctc gac     1968 
Lys Lys Pro Arg Ile Leu Phe Leu Asp Glu Ala Thr Ser His Leu Asp 
                645                 650                 655 

gta cac tgc gaa cag cgg gtc aac gcc gcc att cga gcg ctg cgc atc     2016 
Val His Cys Glu Gln Arg Val Asn Ala Ala Ile Arg Ala Leu Arg Ile 
            660                 665                 670 

acc cgc atc atg gtc gcc cat cgg ccc gag acc atc gcc tcg gcg gac     2064 
Thr Arg Ile Met Val Ala His Arg Pro Glu Thr Ile Ala Ser Ala Asp 
        675                 680                 685 

cgc gtg ata gtc ctc ggc cag ggc aag gta agc ctc gac gaa agc acc     2112 
Arg Val Ile Val Leu Gly Gln Gly Lys Val Ser Leu Asp Glu Ser Thr 
    690                 695                 700 

gcg cgc ctg gcc gaa cgc cag gcc gcc gcg gcg cgg gag cag gcc         2157 
Ala Arg Leu Ala Glu Arg Gln Ala Ala Ala Ala Arg Glu Gln Ala 
705                 710                 715 

tga                                                                 2160 

 
           
             14  
             719  
             PRT  
             Pseudomonas aeruginosa  
           
            14 

Met Ala Phe Leu Asp Ala Leu Ala Leu Arg Leu Gly Arg Arg Leu Pro 
 1               5                  10                  15 

Leu Val Leu Gln Thr Glu Ala Thr Glu Cys Gly Leu Ala Cys Leu Ala 
            20                  25                  30 

Met Ile Ala Gly Tyr His Gly His His Thr Gly Leu Met Glu Leu Arg 
        35                  40                  45 

Arg Arg Phe Ser Val Ser Leu Lys Gly Ile Ser Leu Lys Gln Leu Ile 
    50                  55                  60 

Gln Thr Ala His Arg Leu Gly Leu Gly Thr Arg Ala Val Lys Leu Asp 
65                  70                  75                  80 

Leu Gly Asp Leu Gly Lys Leu Lys Leu Pro Cys Val Leu His Trp Asn 
                85                  90                  95 

Phe Asn His Phe Val Val Leu Lys Ala Val Asp Gly Arg Gly Ala Val 
            100                 105                 110 

Leu His Asp Pro Ala His Gly Gln Arg Arg Leu Gly Leu Glu Glu Val 
        115                 120                 125 

Ser Arg Ser Phe Thr Gly Val Ala Leu Glu Leu Trp Pro Glu Ser Gly 
    130                 135                 140 

Phe Glu Lys Gln Glu Ala Pro Pro Arg Ile Lys Leu Leu Gly Met Leu 
145                 150                 155                 160 

Gly Lys Val Thr Gly Leu Tyr Arg Ser Leu Ala Gln Val Leu Leu Leu 
                165                 170                 175 

Ala Gly Ala Leu Glu Val Phe Ser Leu Ile Ser Pro Phe Phe Leu Gln 
            180                 185                 190 

Trp Thr Ile Asp Asn Val Ile Val Ser Glu Asp Arg Asp Leu Leu Ser 
        195                 200                 205 

Thr Leu Ala Ile Gly Phe Gly Leu Leu Leu Leu Met Gln Gln Ala Val 
    210                 215                 220 

Ser Gly Val Arg Ala Trp Val Met Met His Met Ser Thr Leu Leu Gly 
225                 230                 235                 240 

Val Gln Trp Gln Ala Asn Val Phe Ser His Leu Leu Arg Leu Pro Ala 
                245                 250                 255 

Gln Tyr Phe Glu Lys Arg His Leu Gly Asp Val Val Ser Arg Phe Gly 
            260                 265                 270 

Ala Val Asn Ser Ile Gln Gln Thr Leu Thr Ala Ala Phe Leu Ser Ala 
        275                 280                 285 

Val Leu Asp Gly Leu Met Thr Val Ala Thr Leu Gly Met Met Leu Leu 
    290                 295                 300 

Tyr Ser Pro Pro Leu Ala Ala Ile Ala Ile Ala Ala Met Ser Leu Tyr 
305                 310                 315                 320 

Ala Leu Gly Arg Trp Ile Trp Tyr Arg Pro Leu Arg Asn Ala Thr Glu 
                325                 330                 335 

Glu Gln Ile Val His Ala Ala Arg Gln Gln Ser His Phe Leu Glu Thr 
            340                 345                 350 

Val Arg Gly Ile Arg Pro Leu Lys Leu Phe Gln Arg Gln Asp Glu Arg 
        355                 360                 365 

Arg Ser Val Trp Leu Gly Leu Leu Val Glu Gln Ile Asn Ala Gly Leu 
    370                 375                 380 

Arg Thr Gln Lys Leu Gln Leu Phe Tyr Gln Gln Leu Asn Gly Leu Leu 
385                 390                 395                 400 

Phe Gly Val Glu Asn Leu Leu Val Ile Trp Leu Gly Ala Thr Met Val 
                405                 410                 415 

Met Asp Gly Gln Phe Ser Val Gly Ile Leu Met Ala Phe Asn Ala Tyr 
            420                 425                 430 

Lys Ser Gln Phe Asp Ser Arg Val Gly Ser Leu Ile Asp Lys Phe Phe 
        435                 440                 445 

Glu Leu Arg Met Leu Gln Leu Gln Gly Glu Arg Leu Ala Asp Ile Val 
    450                 455                 460 

Leu Gln Ala Pro Glu Val Ser His Gly Asp Ile Leu Pro Glu Asn Leu 
465                 470                 475                 480 

Arg Glu Arg Glu Ala Ser Ile Glu Ile Gln Gly Leu Arg Tyr Arg Tyr 
                485                 490                 495 

Ala Glu Gln Glu Pro Trp Val Leu Asp Gly Leu Asp Leu Arg Ile Ala 
            500                 505                 510 

Gly Gly Glu Ser Val Ala Ile Val Gly Pro Ser Gly Cys Gly Lys Ser 
        515                 520                 525 

Thr Leu Phe Asn Val Leu Leu Gly Ile Leu Pro Pro Val Glu Gly Gln 
    530                 535                 540 

Ile Arg Met Ala Gly Leu Asp Leu Ala Gln Leu Gly Leu Asp Gly Leu 
545                 550                 555                 560 

Arg Glu Leu Val Gly Thr Val Leu Gln Asp Asp Val Leu Phe Ala Gly 
                565                 570                 575 

Ser Leu Ser Asp Asn Ile Ser Phe Phe Asp Pro Gln Pro Asp Met Pro 
            580                 585                 590 

Trp Leu Leu Gln Cys Ala Gln Met Ala Ala Ile His Asp Asp Ile Gln 
        595                 600                 605 

Ala Met Pro Met Gly Tyr Asn Thr Leu Val Gly Asp Met Gly Thr Val 
    610                 615                 620 

Leu Ser Gly Gly Gln Lys Gln Arg Val Met Leu Ala Arg Ala Leu Tyr 
625                 630                 635                 640 

Lys Lys Pro Arg Ile Leu Phe Leu Asp Glu Ala Thr Ser His Leu Asp 
                645                 650                 655 

Val His Cys Glu Gln Arg Val Asn Ala Ala Ile Arg Ala Leu Arg Ile 
            660                 665                 670 

Thr Arg Ile Met Val Ala His Arg Pro Glu Thr Ile Ala Ser Ala Asp 
        675                 680                 685 

Arg Val Ile Val Leu Gly Gln Gly Lys Val Ser Leu Asp Glu Ser Thr 
    690                 695                 700 

Ala Arg Leu Ala Glu Arg Gln Ala Ala Ala Ala Arg Glu Gln Ala 
705                 710                 715 

 
           
             15  
             1416  
             DNA  
             Pseudomonas aeruginosa  
             
               CDS  
               (1)...(1413)  
             
           
            15 

atg cgt gcc ctc gcc ggc ctg ttg tgc ggc ctg ctc ggc ctg gtt ccc       48 
Met Arg Ala Leu Ala Gly Leu Leu Cys Gly Leu Leu Gly Leu Val Pro 
 1               5                   10                  15 

ggc gcc gcc gcc tac gag ccg gac gtg ttc ggc acc acc ggc cag gtc       96 
Gly Ala Ala Ala Tyr Glu Pro Asp Val Phe Gly Thr Thr Gly Gln Val 
             20                  25                  30 

gcc ggc cag gcg gtc tac gac ctc ggc ggc agc ggt ttg ccc tgc cgc      144 
Ala Gly Gln Ala Val Tyr Asp Leu Gly Gly Ser Gly Leu Pro Cys Arg 
         35                  40                  45 

ggc ggg ccg cca ccg acc gag ctg agc ctg gag gaa gcc atc gag cgg      192 
Gly Gly Pro Pro Pro Thr Glu Leu Ser Leu Glu Glu Ala Ile Glu Arg 
     50                  55                  60 

atc ctc tgc cac gac ccg cag acc cgc ctc gcc tgg gcc aat gcc aag      240 
Ile Leu Cys His Asp Pro Gln Thr Arg Leu Ala Trp Ala Asn Ala Lys 
 65                  70                  75                  80 

gcc cag gcg gcc cag gtc ggg atc ggc aag tcc gcc tac ctg ccg cgc      288 
Ala Gln Ala Ala Gln Val Gly Ile Gly Lys Ser Ala Tyr Leu Pro Arg 
                 85                  90                  95 

ctg gac ggc cgt ctc gac gcc agt cgc ggc tac agc gac atg gat tat      336 
Leu Asp Gly Arg Leu Asp Ala Ser Arg Gly Tyr Ser Asp Met Asp Tyr 
            100                 105                 110 

cgc gat gcc ccc tac ctc tcc ggc gac ggc cat cgc cac cgg cgc ggc      384 
Arg Asp Ala Pro Tyr Leu Ser Gly Asp Gly His Arg His Arg Arg Gly 
        115                 120                 125 

gcc agc ctc caa ttg agc tgg gtg ctg ttc gac ttc ggc cgc cgc agc      432 
Ala Ser Leu Gln Leu Ser Trp Val Leu Phe Asp Phe Gly Arg Arg Ser 
    130                 135                 140 

gcc gcc ctg cgc aac gcc cag cag ttg ctg ctg gcg gcc aac gcc agc      480 
Ala Ala Leu Arg Asn Ala Gln Gln Leu Leu Leu Ala Ala Asn Ala Ser 
145                 150                 155                 160 

cag gac gcg acc ctg cag aac acc ttc gcc ctc gcc gcc cag gcc tac      528 
Gln Asp Ala Thr Leu Gln Asn Thr Phe Ala Leu Ala Ala Gln Ala Tyr 
                165                 170                 175 

tac gac gcc ctc gcc gcc cag cgc agc ctg gcc gcc tcg cgg cag gtc      576 
Tyr Asp Ala Leu Ala Ala Gln Arg Ser Leu Ala Ala Ser Arg Gln Val 
            180                 185                 190 

gcg gag ctg gcg gcg cag aac ctg gaa gcc gcc gac gcc aag tac cgg      624 
Ala Glu Leu Ala Ala Gln Asn Leu Glu Ala Ala Asp Ala Lys Tyr Arg 
        195                 200                 205 

gcc ggc gcc gcc gcc ctt tcc gat cgc ctg cag gcg cag acc gcg ctg      672 
Ala Gly Ala Ala Ala Leu Ser Asp Arg Leu Gln Ala Gln Thr Ala Leu 
    210                 215                 220 

tcc cag gcg agc ctc gcc cag gtc cgc gac gaa ggc gcc ctg agc aac      720 
Ser Gln Ala Ser Leu Ala Gln Val Arg Asp Glu Gly Ala Leu Ser Asn 
225                 230                 235                 240 

gcc ctc ggc gtc atc gcc ctg cgc atg ggc ctg gcg ccg gat acc ccg      768 
Ala Leu Gly Val Ile Ala Leu Arg Met Gly Leu Ala Pro Asp Thr Pro 
                245                 250                 255 

ctg cgc ctc tcc ggc gag ctg gag gcg caa ccc gac acc ggc ttc gtc      816 
Leu Arg Leu Ser Gly Glu Leu Glu Ala Gln Pro Asp Thr Gly Phe Val 
            260                 265                 270 

aag gcc atc gac gag atg ctc gcc gaa gcc cgc cgc gag cat ccg gcg      864 
Lys Ala Ile Asp Glu Met Leu Ala Glu Ala Arg Arg Glu His Pro Ala 
        275                 280                 285 

ctg ctc gcc gcc cag gcg cgg ctg aaa gcc gcc gcc gcc tcg gtg gag      912 
Leu Leu Ala Ala Gln Ala Arg Leu Lys Ala Ala Ala Ala Ser Val Glu 
    290                 295                 300 

gaa agc cgc gcc gcc ggc cgg ccg agc ctg gcg ctg agc gcc aac ctg      960 
Glu Ser Arg Ala Ala Gly Arg Pro Ser Leu Ala Leu Ser Ala Asn Leu 
305                 310                 315                 320 

gca cgc agc cat agc gac cag gcg atg gcg ttc aac ggc gat acc cgc     1008 
Ala Arg Ser His Ser Asp Gln Ala Met Ala Phe Asn Gly Asp Thr Arg 
                325                 330                 335 

gaa cgc gac cgc agc atc ggc ctg caa ctg aac atc ccg ttg ttc gaa     1056 
Glu Arg Asp Arg Ser Ile Gly Leu Gln Leu Asn Ile Pro Leu Phe Glu 
            340                 345                 350 

ggc ttc gaa cgc acc tac cag gtc cgc aac gcc ctg gcc cgc cgc gaa     1104 
Gly Phe Glu Arg Thr Tyr Gln Val Arg Asn Ala Leu Ala Arg Arg Glu 
        355                 360                 365 

gcc agc gaa gcg gag ctg gcc gac acc gag cag cag gtt tcg ctg gag     1152 
Ala Ser Glu Ala Glu Leu Ala Asp Thr Glu Gln Gln Val Ser Leu Glu 
    370                 375                 380 

gtg tgg aac aac tac cag tcg ctc agc gtc gag acc cgc agc ctg gcg     1200 
Val Trp Asn Asn Tyr Gln Ser Leu Ser Val Glu Thr Arg Ser Leu Ala 
385                 390                 395                 400 

cgc acc cgc gaa ctg gtc gaa cag tcg cgg caa agc ctg gag gtg gtg     1248 
Arg Thr Arg Glu Leu Val Glu Gln Ser Arg Gln Ser Leu Glu Val Val 
                405                 410                 415 

cag ggc cgc tac cgc tca ggg gtc ggc agc atg atc gag ctg ctc aac     1296 
Gln Gly Arg Tyr Arg Ser Gly Val Gly Ser Met Ile Glu Leu Leu Asn 
            420                 425                 430 

gcc ctg acc gcc tac gcc agc gcc gag gac cag cac atc cgc gcc ctc     1344 
Ala Leu Thr Ala Tyr Ala Ser Ala Glu Asp Gln His Ile Arg Ala Leu 
        435                 440                 445 

ggc aac tgg cag acc tcg cgc ctg cga ctg gcg gcg agc ctc ggt cgc     1392 
Gly Asn Trp Gln Thr Ser Arg Leu Arg Leu Ala Ala Ser Leu Gly Arg 
    450                 455                 460 

ctg ggt ttc tgg agc ctg cgc tga                                     1416 
Leu Gly Phe Trp Ser Leu Arg 
465                 470 

 
           
             16  
             471  
             PRT  
             Pseudomonas aeruginosa  
           
            16 

Met Arg Ala Leu Ala Gly Leu Leu Cys Gly Leu Leu Gly Leu Val Pro 
 1               5                  10                  15 

Gly Ala Ala Ala Tyr Glu Pro Asp Val Phe Gly Thr Thr Gly Gln Val 
            20                  25                  30 

Ala Gly Gln Ala Val Tyr Asp Leu Gly Gly Ser Gly Leu Pro Cys Arg 
        35                  40                  45 

Gly Gly Pro Pro Pro Thr Glu Leu Ser Leu Glu Glu Ala Ile Glu Arg 
    50                  55                  60 

Ile Leu Cys His Asp Pro Gln Thr Arg Leu Ala Trp Ala Asn Ala Lys 
65                  70                  75                  80 

Ala Gln Ala Ala Gln Val Gly Ile Gly Lys Ser Ala Tyr Leu Pro Arg 
                85                  90                  95 

Leu Asp Gly Arg Leu Asp Ala Ser Arg Gly Tyr Ser Asp Met Asp Tyr 
            100                 105                 110 

Arg Asp Ala Pro Tyr Leu Ser Gly Asp Gly His Arg His Arg Arg Gly 
        115                 120                 125 

Ala Ser Leu Gln Leu Ser Trp Val Leu Phe Asp Phe Gly Arg Arg Ser 
    130                 135                 140 

Ala Ala Leu Arg Asn Ala Gln Gln Leu Leu Leu Ala Ala Asn Ala Ser 
145                 150                 155                 160 

Gln Asp Ala Thr Leu Gln Asn Thr Phe Ala Leu Ala Ala Gln Ala Tyr 
                165                 170                 175 

Tyr Asp Ala Leu Ala Ala Gln Arg Ser Leu Ala Ala Ser Arg Gln Val 
            180                 185                 190 

Ala Glu Leu Ala Ala Gln Asn Leu Glu Ala Ala Asp Ala Lys Tyr Arg 
        195                 200                 205 

Ala Gly Ala Ala Ala Leu Ser Asp Arg Leu Gln Ala Gln Thr Ala Leu 
    210                 215                 220 

Ser Gln Ala Ser Leu Ala Gln Val Arg Asp Glu Gly Ala Leu Ser Asn 
225                 230                 235                 240 

Ala Leu Gly Val Ile Ala Leu Arg Met Gly Leu Ala Pro Asp Thr Pro 
                245                 250                 255 

Leu Arg Leu Ser Gly Glu Leu Glu Ala Gln Pro Asp Thr Gly Phe Val 
            260                 265                 270 

Lys Ala Ile Asp Glu Met Leu Ala Glu Ala Arg Arg Glu His Pro Ala 
        275                 280                 285 

Leu Leu Ala Ala Gln Ala Arg Leu Lys Ala Ala Ala Ala Ser Val Glu 
    290                 295                 300 

Glu Ser Arg Ala Ala Gly Arg Pro Ser Leu Ala Leu Ser Ala Asn Leu 
305                 310                 315                 320 

Ala Arg Ser His Ser Asp Gln Ala Met Ala Phe Asn Gly Asp Thr Arg 
                325                 330                 335 

Glu Arg Asp Arg Ser Ile Gly Leu Gln Leu Asn Ile Pro Leu Phe Glu 
            340                 345                 350 

Gly Phe Glu Arg Thr Tyr Gln Val Arg Asn Ala Leu Ala Arg Arg Glu 
        355                 360                 365 

Ala Ser Glu Ala Glu Leu Ala Asp Thr Glu Gln Gln Val Ser Leu Glu 
    370                 375                 380 

Val Trp Asn Asn Tyr Gln Ser Leu Ser Val Glu Thr Arg Ser Leu Ala 
385                 390                 395                 400 

Arg Thr Arg Glu Leu Val Glu Gln Ser Arg Gln Ser Leu Glu Val Val 
                405                 410                 415 

Gln Gly Arg Tyr Arg Ser Gly Val Gly Ser Met Ile Glu Leu Leu Asn 
            420                 425                 430 

Ala Leu Thr Ala Tyr Ala Ser Ala Glu Asp Gln His Ile Arg Ala Leu 
        435                 440                 445 

Gly Asn Trp Gln Thr Ser Arg Leu Arg Leu Ala Ala Ser Leu Gly Arg 
    450                 455                 460 

Leu Gly Phe Trp Ser Leu Arg 
465                 470 

 
           
             17  
             1176  
             DNA  
             Pseudomonas aeruginosa  
             
               CDS  
               (1)...(1173)  
             
           
            17 

atg aga cga acc cgt agt act cgt cgc gca ctg ctc gtc gca gtc tgc       48 
Met Arg Arg Thr Arg Ser Thr Arg Arg Ala Leu Leu Val Ala Val Cys 
 1               5                   10                  15 

ctc agc ccc ctg atc gcc ctg gcc gcc tgg cag gcc tat ccg ttc cgc       96 
Leu Ser Pro Leu Ile Ala Leu Ala Ala Trp Gln Ala Tyr Pro Phe Arg 
             20                  25                  30 

agc aac aac ttc gat acc gtg agc gtc agc cgc ggc agc atc gag agc      144 
Ser Asn Asn Phe Asp Thr Val Ser Val Ser Arg Gly Ser Ile Glu Ser 
         35                  40                  45 

agc gtc tcg gcg ctc ggc acc ctg caa ccg cgg cgc tac gtc gac gtc      192 
Ser Val Ser Ala Leu Gly Thr Leu Gln Pro Arg Arg Tyr Val Asp Val 
     50                  55                  60 

ggc gcc cag gcc tcc ggg cag atc cgc aag ttg cac gtc gag gcc ggg      240 
Gly Ala Gln Ala Ser Gly Gln Ile Arg Lys Leu His Val Glu Ala Gly 
 65                  70                  75                  80 

gac gat gtg acg gaa ggc cag ttg ctg gtc gag atc gac ccc tcc acc      288 
Asp Asp Val Thr Glu Gly Gln Leu Leu Val Glu Ile Asp Pro Ser Thr 
                 85                  90                  95 

cag cag gcc aag gtc gat gcc ggc cgc tat tcg atc gag atg ctc aag      336 
Gln Gln Ala Lys Val Asp Ala Gly Arg Tyr Ser Ile Glu Met Leu Lys 
            100                 105                 110 

gcc caa ctg gcc gag caa cgt gcc cag tac acc ctc gcc cgc cag cag      384 
Ala Gln Leu Ala Glu Gln Arg Ala Gln Tyr Thr Leu Ala Arg Gln Gln 
        115                 120                 125 

tac cag cgc cag cag cgg ctg gcc gcc ggc ggc gca acg cgt acc gag      432 
Tyr Gln Arg Gln Gln Arg Leu Ala Ala Gly Gly Ala Thr Arg Thr Glu 
    130                 135                 140 

gac gtg cag agc gcc cag gcg cag atg ctc gcc acc cag gcg cgg atc      480 
Asp Val Gln Ser Ala Gln Ala Gln Met Leu Ala Thr Gln Ala Arg Ile 
145                 150                 155                 160 

gag atg tac cag gcg cag atc cgc cag gcc cag gcc tcg ttg cgc agc      528 
Glu Met Tyr Gln Ala Gln Ile Arg Gln Ala Gln Ala Ser Leu Arg Ser 
                165                 170                 175 

gac gaa gcc gaa ctc ggc tat acc cgc atc tac gcg ccg atg tcc ggc      576 
Asp Glu Ala Glu Leu Gly Tyr Thr Arg Ile Tyr Ala Pro Met Ser Gly 
            180                 185                 190 

acg gtg gtg gcg gtc gat gcg cgc gaa ggc cag acc ctc aat gcc cag      624 
Thr Val Val Ala Val Asp Ala Arg Glu Gly Gln Thr Leu Asn Ala Gln 
        195                 200                 205 

cag cag acc ccg ttg atc ctg cgg atc gcc aaa ttg tcg ccg atg acc      672 
Gln Gln Thr Pro Leu Ile Leu Arg Ile Ala Lys Leu Ser Pro Met Thr 
    210                 215                 220 

gtc tgg gcc cag gtt tcg gaa gcc gac atc ggc cgg gtc aag ccc ggc      720 
Val Trp Ala Gln Val Ser Glu Ala Asp Ile Gly Arg Val Lys Pro Gly 
225                 230                 235                 240 

atg ccg gcc tac ttc acg acc ctc agc ggc gaa ggc cgg cgc tgg acc      768 
Met Pro Ala Tyr Phe Thr Thr Leu Ser Gly Glu Gly Arg Arg Trp Thr 
                245                 250                 255 

ggc aag gtc cgg cag atc ctc ccg gtg ccg ccc aag ccg ctg gac cag      816 
Gly Lys Val Arg Gln Ile Leu Pro Val Pro Pro Lys Pro Leu Asp Gln 
            260                 265                 270 

agc aac cag ggc ggc ggc agc ccc acc agc ggc agc ggc ggg cag agc      864 
Ser Asn Gln Gly Gly Gly Ser Pro Thr Ser Gly Ser Gly Gly Gln Ser 
        275                 280                 285 

ggc agc ggc cgg gtg gtg ctg tat acc gtg ctg gtc gac gtg gac aac      912 
Gly Ser Gly Arg Val Val Leu Tyr Thr Val Leu Val Asp Val Asp Asn 
    290                 295                 300 

ggc gac cac caa ctg atg gcg gaa atg acc gcc cag gtg ttc ttc gtc      960 
Gly Asp His Gln Leu Met Ala Glu Met Thr Ala Gln Val Phe Phe Val 
305                 310                 315                 320 

gcc gcc acc gca gaa aac atc ctc acc gcg ccg gtc gcc gcc atc cac     1008 
Ala Ala Thr Ala Glu Asn Ile Leu Thr Ala Pro Val Ala Ala Ile His 
                325                 330                 335 

gac gac ggc aag ggc ggc cag gtc gcc tgg gtg gtc ggc agc aac ggc     1056 
Asp Asp Gly Lys Gly Gly Gln Val Ala Trp Val Val Gly Ser Asn Gly 
            340                 345                 350 

aag ccg cag agc cgc cag atc agg acc ggc atc agc gac cgc ctg cgg     1104 
Lys Pro Gln Ser Arg Gln Ile Arg Thr Gly Ile Ser Asp Arg Leu Arg 
        355                 360                 365 

gta cag gtg ctt gcc ggc ctg gag gaa ggc gac cgc ctg ttg atg gcc     1152 
Val Gln Val Leu Ala Gly Leu Glu Glu Gly Asp Arg Leu Leu Met Ala 
    370                 375                 380 

gct ccc gac ggc agc gac agc tga                                     1176 
Ala Pro Asp Gly Ser Asp Ser 
385                 390  
           
             18  
             391  
             PRT  
             Pseudomonas aeruginosa  
           
            18 

Met Arg Arg Thr Arg Ser Thr Arg Arg Ala Leu Leu Val Ala Val Cys 
 1               5                  10                  15 

Leu Ser Pro Leu Ile Ala Leu Ala Ala Trp Gln Ala Tyr Pro Phe Arg 
            20                  25                  30 

Ser Asn Asn Phe Asp Thr Val Ser Val Ser Arg Gly Ser Ile Glu Ser 
        35                  40                  45 

Ser Val Ser Ala Leu Gly Thr Leu Gln Pro Arg Arg Tyr Val Asp Val 
    50                  55                  60 

Gly Ala Gln Ala Ser Gly Gln Ile Arg Lys Leu His Val Glu Ala Gly 
65                  70                  75                  80 

Asp Asp Val Thr Glu Gly Gln Leu Leu Val Glu Ile Asp Pro Ser Thr 
                85                  90                  95 

Gln Gln Ala Lys Val Asp Ala Gly Arg Tyr Ser Ile Glu Met Leu Lys 
            100                 105                 110 

Ala Gln Leu Ala Glu Gln Arg Ala Gln Tyr Thr Leu Ala Arg Gln Gln 
        115                 120                 125 

Tyr Gln Arg Gln Gln Arg Leu Ala Ala Gly Gly Ala Thr Arg Thr Glu 
    130                 135                 140 

Asp Val Gln Ser Ala Gln Ala Gln Met Leu Ala Thr Gln Ala Arg Ile 
145                 150                 155                 160 

Glu Met Tyr Gln Ala Gln Ile Arg Gln Ala Gln Ala Ser Leu Arg Ser 
                165                 170                 175 

Asp Glu Ala Glu Leu Gly Tyr Thr Arg Ile Tyr Ala Pro Met Ser Gly 
            180                 185                 190 

Thr Val Val Ala Val Asp Ala Arg Glu Gly Gln Thr Leu Asn Ala Gln 
        195                 200                 205 

Gln Gln Thr Pro Leu Ile Leu Arg Ile Ala Lys Leu Ser Pro Met Thr 
    210                 215                 220 

Val Trp Ala Gln Val Ser Glu Ala Asp Ile Gly Arg Val Lys Pro Gly 
225                 230                 235                 240 

Met Pro Ala Tyr Phe Thr Thr Leu Ser Gly Glu Gly Arg Arg Trp Thr 
                245                 250                 255 

Gly Lys Val Arg Gln Ile Leu Pro Val Pro Pro Lys Pro Leu Asp Gln 
            260                 265                 270 

Ser Asn Gln Gly Gly Gly Ser Pro Thr Ser Gly Ser Gly Gly Gln Ser 
        275                 280                 285 

Gly Ser Gly Arg Val Val Leu Tyr Thr Val Leu Val Asp Val Asp Asn 
    290                 295                 300 

Gly Asp His Gln Leu Met Ala Glu Met Thr Ala Gln Val Phe Phe Val 
305                 310                 315                 320 

Ala Ala Thr Ala Glu Asn Ile Leu Thr Ala Pro Val Ala Ala Ile His 
                325                 330                 335 

Asp Asp Gly Lys Gly Gly Gln Val Ala Trp Val Val Gly Ser Asn Gly 
            340                 345                 350 

Lys Pro Gln Ser Arg Gln Ile Arg Thr Gly Ile Ser Asp Arg Leu Arg 
        355                 360                 365 

Val Gln Val Leu Ala Gly Leu Glu Glu Gly Asp Arg Leu Leu Met Ala 
    370                 375                 380 

Ala Pro Asp Gly Ser Asp Ser 
385                 390 

 
           
             19  
             1992  
             DNA  
             Pseudomonas aeruginosa  
             
               CDS  
               (1)...(1989)  
             
           
            19 

atg gaa aac gcc acg caa ccc gtc ccc ctg atc gaa ctg cgc gac atc       48 
Met Glu Asn Ala Thr Gln Pro Val Pro Leu Ile Glu Leu Arg Asp Ile 
 1               5                   10                  15 

cgc aag cgc tac ggc ggc aat ggc acc ccg gaa gtc gag gta ctc aag       96 
Arg Lys Arg Tyr Gly Gly Asn Gly Thr Pro Glu Val Glu Val Leu Lys 
             20                  25                  30 

ggc gta tcg ctg tcg atc cac gcc ggc gag ttc gtc gcc atc gtc ggc      144 
Gly Val Ser Leu Ser Ile His Ala Gly Glu Phe Val Ala Ile Val Gly 
         35                  40                  45 

gcc tcc ggc tcc ggc aag tcg acc ctg atg aac atc ctc ggc tgc ctc      192 
Ala Ser Gly Ser Gly Lys Ser Thr Leu Met Asn Ile Leu Gly Cys Leu 
     50                  55                  60 

gac cgg ccc agc tcc ggc agc tac cac ttc gcc ggc cac gac gtc gcc      240 
Asp Arg Pro Ser Ser Gly Ser Tyr His Phe Ala Gly His Asp Val Ala 
 65                  70                  75                  80 

gaa ctg gac agc gac gag cag gcc tgg ctg cgc cgc gag gca ttc ggc      288 
Glu Leu Asp Ser Asp Glu Gln Ala Trp Leu Arg Arg Glu Ala Phe Gly 
                 85                  90                  95 

ttc gtg ttc cag ggc tat cac ctg atc ccc tcc gcc tcg gcc cag gaa      336 
Phe Val Phe Gln Gly Tyr His Leu Ile Pro Ser Ala Ser Ala Gln Glu 
            100                 105                 110 

aac gtc gag atg ccg gcg atc tac gcc ggc atc ccg gcg agc gag cgg      384 
Asn Val Glu Met Pro Ala Ile Tyr Ala Gly Ile Pro Ala Ser Glu Arg 
        115                 120                 125 

cac acc cgc gcg cgg gcc ctg ctc gaa cgc ctg ggc ctg gcc gag cgc      432 
His Thr Arg Ala Arg Ala Leu Leu Glu Arg Leu Gly Leu Ala Glu Arg 
    130                 135                 140 

acc gcc aac cgt ccg cac cag ttg tcc ggc ggc cag cag cag cgg gtg      480 
Thr Ala Asn Arg Pro His Gln Leu Ser Gly Gly Gln Gln Gln Arg Val 
145                 150                 155                 160 

tcg atc gcc cgc gcg ctg atg aac ggc ggc cat atc atc ctc gcc gac      528 
Ser Ile Ala Arg Ala Leu Met Asn Gly Gly His Ile Ile Leu Ala Asp 
                165                 170                 175 

gaa ccc acc ggc gcc ctc gac agc cac agc ggc gcg gaa gtc atg gcg      576 
Glu Pro Thr Gly Ala Leu Asp Ser His Ser Gly Ala Glu Val Met Ala 
            180                 185                 190 

ctg ctc gac gag ctg gcc agc cag ggc cac gtg gtg atc ctg atc acc      624 
Leu Leu Asp Glu Leu Ala Ser Gln Gly His Val Val Ile Leu Ile Thr 
        195                 200                 205 

cac gac cgc gac gtc gcc gcc cgc gcc aag cgc atc atc gag gtg cgc      672 
His Asp Arg Asp Val Ala Ala Arg Ala Lys Arg Ile Ile Glu Val Arg 
    210                 215                 220 

gac ggc gag atc gtc agc gac agc gcc aac gac gag cgc ccg gcg cac      720 
Asp Gly Glu Ile Val Ser Asp Ser Ala Asn Asp Glu Arg Pro Ala His 
225                 230                 235                 240 

ccg agc gcc ggc gtc gag cgc cac ctg cag gcc gac gat ctc agc cag      768 
Pro Ser Ala Gly Val Glu Arg His Leu Gln Ala Asp Asp Leu Ser Gln 
                245                 250                 255 

cgc ctc gcc gag ggc agc agc gaa ccc tcg ggg gcc tgg cgc gcc gaa      816 
Arg Leu Ala Glu Gly Ser Ser Glu Pro Ser Gly Ala Trp Arg Ala Glu 
            260                 265                 270 

ctg ctg gag gcg gtg cgc gcc gcc tgg cgg gtg atg tgg atc aat cgg      864 
Leu Leu Glu Ala Val Arg Ala Ala Trp Arg Val Met Trp Ile Asn Arg 
        275                 280                 285 

ttc cgc acc gcg ctg acc ctg ctc ggg atc atc atc ggc gtc gcc tcg      912 
Phe Arg Thr Ala Leu Thr Leu Leu Gly Ile Ile Ile Gly Val Ala Ser 
    290                 295                 300 

gtg gtg gtc atg ctc gcc gtc ggc gag ggc agc aag cgc cag gtg atg      960 
Val Val Val Met Leu Ala Val Gly Glu Gly Ser Lys Arg Gln Val Met 
305                 310                 315                 320 

gcg cag atg ggc gcg ttc ggc tcg aac atc atc tat ctc agc ggc tac     1008 
Ala Gln Met Gly Ala Phe Gly Ser Asn Ile Ile Tyr Leu Ser Gly Tyr 
                325                 330                 335 

tcg ccg aac ccg cgc gcg ccg atg ggc atc gtc agc agc gac gac gtc     1056 
Ser Pro Asn Pro Arg Ala Pro Met Gly Ile Val Ser Ser Asp Asp Val 
            340                 345                 350 

gcc gcc atc gcc acc ctg ccc cag gtg aag aag gtc atg ccg gtg aac     1104 
Ala Ala Ile Ala Thr Leu Pro Gln Val Lys Lys Val Met Pro Val Asn 
        355                 360                 365 

ggc ggc gag ctg gtg gtg cgc tac ggg aac atc gac tac cac gcc tac     1152 
Gly Gly Glu Leu Val Val Arg Tyr Gly Asn Ile Asp Tyr His Ala Tyr 
    370                 375                 380 

gtc ggc ggc aac aac acc gac ttc ccg gaa atc ctc aac tgg ccg gtg     1200 
Val Gly Gly Asn Asn Thr Asp Phe Pro Glu Ile Leu Asn Trp Pro Val 
385                 390                 395                 400 

gcc gag ggc agc tac ttc acc gag cgc gac gaa gac gcc gcc acc acg     1248 
Ala Glu Gly Ser Tyr Phe Thr Glu Arg Asp Glu Asp Ala Ala Thr Thr 
                405                 410                 415 

gtc gcg gtg atc ggc tac aag gtg cgc aag aag ctg ttc ggc agc gcc     1296 
Val Ala Val Ile Gly Tyr Lys Val Arg Lys Lys Leu Phe Gly Ser Ala 
            420                 425                 430 

aac ccg atc ggc cgc tac atc ctc atc gag aac gtg ccg ttc cag gtc     1344 
Asn Pro Ile Gly Arg Tyr Ile Leu Ile Glu Asn Val Pro Phe Gln Val 
        435                 440                 445 

atc ggc gtg ctc gcc gag aaa ggc tcc agc tcc ggc gac aag gat gcc     1392 
Ile Gly Val Leu Ala Glu Lys Gly Ser Ser Ser Gly Asp Lys Asp Ala 
    450                 455                 460 

gac aac cgc atc gcc atc ccc tac tcc gct gcc agc atc cgc ctg ttc     1440 
Asp Asn Arg Ile Ala Ile Pro Tyr Ser Ala Ala Ser Ile Arg Leu Phe 
465                 470                 475                 480 

ggc acg cgc aac ccc gag tac gtg atc atc gcc gcc gcc gac gcc cag     1488 
Gly Thr Arg Asn Pro Glu Tyr Val Ile Ile Ala Ala Ala Asp Ala Gln 
                485                 490                 495 

cgc gtg cac cag gcc gaa cgc gcc atc gac cag ttg atg ctg cgc ctg     1536 
Arg Val His Gln Ala Glu Arg Ala Ile Asp Gln Leu Met Leu Arg Leu 
            500                 505                 510 

cac cgc ggc cag cgc gac tac gag ctg acc aac aac gcg gcg atg atc     1584 
His Arg Gly Gln Arg Asp Tyr Glu Leu Thr Asn Asn Ala Ala Met Ile 
        515                 520                 525 

cag gcc gag gcg aag acc cag aac acc ctg tcg ctg atg ctc ggc tcg     1632 
Gln Ala Glu Ala Lys Thr Gln Asn Thr Leu Ser Leu Met Leu Gly Ser 
    530                 535                 540 

atc gcc gcg atc tcc ctg ctg gta ggc ggg atc ggc gtg atg aac atc     1680 
Ile Ala Ala Ile Ser Leu Leu Val Gly Gly Ile Gly Val Met Asn Ile 
545                 550                 555                 560 

atg ctc atg acc gtg cgc gaa cgc acc cgc gag atc ggc atc cgc atg     1728 
Met Leu Met Thr Val Arg Glu Arg Thr Arg Glu Ile Gly Ile Arg Met 
                565                 570                 575 

gcc act ggc gcc cgc cag ggc gat atc ctc cgc cag ttc ctc acc gag     1776 
Ala Thr Gly Ala Arg Gln Gly Asp Ile Leu Arg Gln Phe Leu Thr Glu 
            580                 585                 590 

gcg gcg atg ctc tcg gtg gtc ggc ggc ctg gcc ggg atc gcc ctg gcc     1824 
Ala Ala Met Leu Ser Val Val Gly Gly Leu Ala Gly Ile Ala Leu Ala 
        595                 600                 605 

ctg tgc atc ggc ggc gtg ctg ctg ctc ggc cag gtc gcg gtg gcc ttt     1872 
Leu Cys Ile Gly Gly Val Leu Leu Leu Gly Gln Val Ala Val Ala Phe 
    610                 615                 620 

tcc ctg tcg gcc atc gtc ggc gcc ttc agt tgc gcg ctg gtc acc ggc     1920 
Ser Leu Ser Ala Ile Val Gly Ala Phe Ser Cys Ala Leu Val Thr Gly 
625                 630                 635                 640 

ctg gtg ttc ggc ttc atg ccg gcg cgc aag gcc gcc cag ctg gac ccg     1968 
Leu Val Phe Gly Phe Met Pro Ala Arg Lys Ala Ala Gln Leu Asp Pro 
                645                 650                 655 

gtg gcc gcc ctg gcc agc caa tga                                     1992 
Val Ala Ala Leu Ala Ser Gln 
            660 

 
           
             20  
             663  
             PRT  
             Pseudomonas aeruginosa  
           
            20 

Met Glu Asn Ala Thr Gln Pro Val Pro Leu Ile Glu Leu Arg Asp Ile 
 1               5                  10                  15 

Arg Lys Arg Tyr Gly Gly Asn Gly Thr Pro Glu Val Glu Val Leu Lys 
            20                  25                  30 

Gly Val Ser Leu Ser Ile His Ala Gly Glu Phe Val Ala Ile Val Gly 
        35                  40                  45 

Ala Ser Gly Ser Gly Lys Ser Thr Leu Met Asn Ile Leu Gly Cys Leu 
    50                  55                  60 

Asp Arg Pro Ser Ser Gly Ser Tyr His Phe Ala Gly His Asp Val Ala 
65                  70                  75                  80 

Glu Leu Asp Ser Asp Glu Gln Ala Trp Leu Arg Arg Glu Ala Phe Gly 
                85                  90                  95 

Phe Val Phe Gln Gly Tyr His Leu Ile Pro Ser Ala Ser Ala Gln Glu 
            100                 105                 110 

Asn Val Glu Met Pro Ala Ile Tyr Ala Gly Ile Pro Ala Ser Glu Arg 
        115                 120                 125 

His Thr Arg Ala Arg Ala Leu Leu Glu Arg Leu Gly Leu Ala Glu Arg 
    130                 135                 140 

Thr Ala Asn Arg Pro His Gln Leu Ser Gly Gly Gln Gln Gln Arg Val 
145                 150                 155                 160 

Ser Ile Ala Arg Ala Leu Met Asn Gly Gly His Ile Ile Leu Ala Asp 
                165                 170                 175 

Glu Pro Thr Gly Ala Leu Asp Ser His Ser Gly Ala Glu Val Met Ala 
            180                 185                 190 

Leu Leu Asp Glu Leu Ala Ser Gln Gly His Val Val Ile Leu Ile Thr 
        195                 200                 205 

His Asp Arg Asp Val Ala Ala Arg Ala Lys Arg Ile Ile Glu Val Arg 
    210                 215                 220 

Asp Gly Glu Ile Val Ser Asp Ser Ala Asn Asp Glu Arg Pro Ala His 
225                 230                 235                 240 

Pro Ser Ala Gly Val Glu Arg His Leu Gln Ala Asp Asp Leu Ser Gln 
                245                 250                 255 

Arg Leu Ala Glu Gly Ser Ser Glu Pro Ser Gly Ala Trp Arg Ala Glu 
            260                 265                 270 

Leu Leu Glu Ala Val Arg Ala Ala Trp Arg Val Met Trp Ile Asn Arg 
        275                 280                 285 

Phe Arg Thr Ala Leu Thr Leu Leu Gly Ile Ile Ile Gly Val Ala Ser 
    290                 295                 300 

Val Val Val Met Leu Ala Val Gly Glu Gly Ser Lys Arg Gln Val Met 
305                 310                 315                 320 

Ala Gln Met Gly Ala Phe Gly Ser Asn Ile Ile Tyr Leu Ser Gly Tyr 
                325                 330                 335 

Ser Pro Asn Pro Arg Ala Pro Met Gly Ile Val Ser Ser Asp Asp Val 
            340                 345                 350 

Ala Ala Ile Ala Thr Leu Pro Gln Val Lys Lys Val Met Pro Val Asn 
        355                 360                 365 

Gly Gly Glu Leu Val Val Arg Tyr Gly Asn Ile Asp Tyr His Ala Tyr 
    370                 375                 380 

Val Gly Gly Asn Asn Thr Asp Phe Pro Glu Ile Leu Asn Trp Pro Val 
385                 390                 395                 400 

Ala Glu Gly Ser Tyr Phe Thr Glu Arg Asp Glu Asp Ala Ala Thr Thr 
                405                 410                 415 

Val Ala Val Ile Gly Tyr Lys Val Arg Lys Lys Leu Phe Gly Ser Ala 
            420                 425                 430 

Asn Pro Ile Gly Arg Tyr Ile Leu Ile Glu Asn Val Pro Phe Gln Val 
        435                 440                 445 

Ile Gly Val Leu Ala Glu Lys Gly Ser Ser Ser Gly Asp Lys Asp Ala 
    450                 455                 460 

Asp Asn Arg Ile Ala Ile Pro Tyr Ser Ala Ala Ser Ile Arg Leu Phe 
465                 470                 475                 480 

Gly Thr Arg Asn Pro Glu Tyr Val Ile Ile Ala Ala Ala Asp Ala Gln 
                485                 490                 495 

Arg Val His Gln Ala Glu Arg Ala Ile Asp Gln Leu Met Leu Arg Leu 
            500                 505                 510 

His Arg Gly Gln Arg Asp Tyr Glu Leu Thr Asn Asn Ala Ala Met Ile 
        515                 520                 525 

Gln Ala Glu Ala Lys Thr Gln Asn Thr Leu Ser Leu Met Leu Gly Ser 
    530                 535                 540 

Ile Ala Ala Ile Ser Leu Leu Val Gly Gly Ile Gly Val Met Asn Ile 
545                 550                 555                 560 

Met Leu Met Thr Val Arg Glu Arg Thr Arg Glu Ile Gly Ile Arg Met 
                565                 570                 575 

Ala Thr Gly Ala Arg Gln Gly Asp Ile Leu Arg Gln Phe Leu Thr Glu 
            580                 585                 590 

Ala Ala Met Leu Ser Val Val Gly Gly Leu Ala Gly Ile Ala Leu Ala 
        595                 600                 605 

Leu Cys Ile Gly Gly Val Leu Leu Leu Gly Gln Val Ala Val Ala Phe 
    610                 615                 620 

Ser Leu Ser Ala Ile Val Gly Ala Phe Ser Cys Ala Leu Val Thr Gly 
625                 630                 635                 640 

Leu Val Phe Gly Phe Met Pro Ala Arg Lys Ala Ala Gln Leu Asp Pro 
                645                 650                 655 

Val Ala Ala Leu Ala Ser Gln 
            660 

 
           
             21  
             1425  
             DNA  
             Pseudomonas aeruginosa  
             
               CDS  
               (1)...(1422)  
             
           
            21 

atg tcc atg aag aat ctc tcc ctg att tcc gcc tgc ctg ctg ctc ggc       48 
Met Ser Met Lys Asn Leu Ser Leu Ile Ser Ala Cys Leu Leu Leu Gly 
 1               5                   10                  15 

gcc tgc ggc agc acg ccg gcg ccc ctc gac agc ggc ctg gcc gcg ccc       96 
Ala Cys Gly Ser Thr Pro Ala Pro Leu Asp Ser Gly Leu Ala Ala Pro 
             20                  25                  30 

agc cag tgg cgc tac ctg gcg gcc ggg cgc agc gat gcc agc gac atc      144 
Ser Gln Trp Arg Tyr Leu Ala Ala Gly Arg Ser Asp Ala Ser Asp Ile 
         35                  40                  45 

cgc cag tgg tgg aag gcc ttc ggc gcg ccg gaa ctg gac agc ctg ctg      192 
Arg Gln Trp Trp Lys Ala Phe Gly Ala Pro Glu Leu Asp Ser Leu Leu 
     50                  55                  60 

caa cgc gcc ctg ctg aac agc cag gac ctc ggc gcg gcg gtg gcc cgc      240 
Gln Arg Ala Leu Leu Asn Ser Gln Asp Leu Gly Ala Ala Val Ala Arg 
 65                  70                  75                  80 

gta cgc cag gcc cag gcc tcg gcg gtg atc gcc ggc gcg ccg ttg ctg      288 
Val Arg Gln Ala Gln Ala Ser Ala Val Ile Ala Gly Ala Pro Leu Leu 
                 85                  90                  95 

ccg gag ctg aat gcg acg ctc ggc gcc agc cgg cag aaa ctc ctg cgc      336 
Pro Glu Leu Asn Ala Thr Leu Gly Ala Ser Arg Gln Lys Leu Leu Arg 
            100                 105                 110 

gac tcg ggc tac agc ggt acc gac gcg acc tcc gac aac gat gcc gtc      384 
Asp Ser Gly Tyr Ser Gly Thr Asp Ala Thr Ser Asp Asn Asp Ala Val 
        115                 120                 125 

gac tcc ttc tcc gcc ggc ctc agc gcc agc tac gaa gtg gac ttc tgg      432 
Asp Ser Phe Ser Ala Gly Leu Ser Ala Ser Tyr Glu Val Asp Phe Trp 
    130                 135                 140 

ggc ggt cgc cag gct gcc tac cgc agc gcc ctg gaa agc ctc aag gcc      480 
Gly Gly Arg Gln Ala Ala Tyr Arg Ser Ala Leu Glu Ser Leu Lys Ala 
145                 150                 155                 160 

agc gag tac gac cgc gcc acg gta gag ctg acc ctg ctc tcc ggc gtc      528 
Ser Glu Tyr Asp Arg Ala Thr Val Glu Leu Thr Leu Leu Ser Gly Val 
                165                 170                 175 

gcc aac agc tac ctg cag gta ttg gcg ctg cgc gaa cag cag cgc atc      576 
Ala Asn Ser Tyr Leu Gln Val Leu Ala Leu Arg Glu Gln Gln Arg Ile 
            180                 185                 190 

gcc agg ctc aac ctg gac aac gcc gag cac gtc ctg cgc ctg gtg gag      624 
Ala Arg Leu Asn Leu Asp Asn Ala Glu His Val Leu Arg Leu Val Glu 
        195                 200                 205 

acc cgc cat gcc gcg ggc tcg gcc acc gcc ctg gag gtc gcc caa cag      672 
Thr Arg His Ala Ala Gly Ser Ala Thr Ala Leu Glu Val Ala Gln Gln 
    210                 215                 220 

agc agc ctg gtc gcc agc cag cgc aag cag ctg ccg ctg ctc gag cag      720 
Ser Ser Leu Val Ala Ser Gln Arg Lys Gln Leu Pro Leu Leu Glu Gln 
225                 230                 235                 240 

cag gcc cat gag gcg ctg att acc ctg gcc acc ctg atc ggc gag ccg      768 
Gln Ala His Glu Ala Leu Ile Thr Leu Ala Thr Leu Ile Gly Glu Pro 
                245                 250                 255 

gtg cag gcg cta cag gtg gcc gag cgg cct ttc gac agc ctg cgc tgg      816 
Val Gln Ala Leu Gln Val Ala Glu Arg Pro Phe Asp Ser Leu Arg Trp 
            260                 265                 270 

ccg gag acc gga gcg ggc ctg ccg agc gaa ctg ctc agc cgc cgt ccc      864 
Pro Glu Thr Gly Ala Gly Leu Pro Ser Glu Leu Leu Ser Arg Arg Pro 
        275                 280                 285 

gat atc gcc aac gcc gaa gcg caa ctg gcc gcg gcc cag gcc gac gtg      912 
Asp Ile Ala Asn Ala Glu Ala Gln Leu Ala Ala Ala Gln Ala Asp Val 
    290                 295                 300 

cag gtg gcg cgc gcg gcg ctg ttc ccc aag ctg acc ctg agc gcc tcg      960 
Gln Val Ala Arg Ala Ala Leu Phe Pro Lys Leu Thr Leu Ser Ala Ser 
305                 310                 315                 320 

ctg tcg tcc ggc gcc aac cgc gcc gcc gac act ttc cgc aac ccc tat     1008 
Leu Ser Ser Gly Ala Asn Arg Ala Ala Asp Thr Phe Arg Asn Pro Tyr 
                325                 330                 335 

tac aac ctg ggc gcc aac ctg ctc gcc ccg atc ttc aac cac ggc cgc     1056 
Tyr Asn Leu Gly Ala Asn Leu Leu Ala Pro Ile Phe Asn His Gly Arg 
            340                 345                 350 

ctg cgc gcc gag cgc gac cgc agc ctg gcg cgc cag gaa gaa ctg ctg     1104 
Leu Arg Ala Glu Arg Asp Arg Ser Leu Ala Arg Gln Glu Glu Leu Leu 
        355                 360                 365 

gaa acc tac cgc aag gcg atc ctc acc gcc ttt gcc gac acc gaa cgc     1152 
Glu Thr Tyr Arg Lys Ala Ile Leu Thr Ala Phe Ala Asp Thr Glu Arg 
    370                 375                 380 

tcg ctg aac agc atc gac ggc ctc gac cgc cag ctg cac tgg caa cag     1200 
Ser Leu Asn Ser Ile Asp Gly Leu Asp Arg Gln Leu His Trp Gln Gln 
385                 390                 395                 400 

cag gag ctg gag cag gcg cag cgc gcc ttc gat ctc tcc gac agc cgc     1248 
Gln Glu Leu Glu Gln Ala Gln Arg Ala Phe Asp Leu Ser Asp Ser Arg 
                405                 410                 415 

tac cag gcc ggc gcg gaa acc ctg ctg acg gtc ctc gaa acg caa cgc     1296 
Tyr Gln Ala Gly Ala Glu Thr Leu Leu Thr Val Leu Glu Thr Gln Arg 
            420                 425                 430 

acg ctg tac gcg gcg cag gat gcc gcc gtg caa ctg cga ctg gcc cgc     1344 
Thr Leu Tyr Ala Ala Gln Asp Ala Ala Val Gln Leu Arg Leu Ala Arg 
        435                 440                 445 

ctg cag gcc tcg gtc ggc ctg tac aag gcc ctc ggc ggc ggc tgg cag     1392 
Leu Gln Ala Ser Val Gly Leu Tyr Lys Ala Leu Gly Gly Gly Trp Gln 
    450                 455                 460 

agc gac cgc cag ggt ctc gcg cgg aaa gac tga                         1425 
Ser Asp Arg Gln Gly Leu Ala Arg Lys Asp 
465                 470 

 
           
             22  
             474  
             PRT  
             Pseudomonas aeruginosa  
           
            22 

Met Ser Met Lys Asn Leu Ser Leu Ile Ser Ala Cys Leu Leu Leu Gly 
 1               5                  10                  15 

Ala Cys Gly Ser Thr Pro Ala Pro Leu Asp Ser Gly Leu Ala Ala Pro 
            20                  25                  30 

Ser Gln Trp Arg Tyr Leu Ala Ala Gly Arg Ser Asp Ala Ser Asp Ile 
        35                  40                  45 

Arg Gln Trp Trp Lys Ala Phe Gly Ala Pro Glu Leu Asp Ser Leu Leu 
    50                  55                  60 

Gln Arg Ala Leu Leu Asn Ser Gln Asp Leu Gly Ala Ala Val Ala Arg 
65                  70                  75                  80 

Val Arg Gln Ala Gln Ala Ser Ala Val Ile Ala Gly Ala Pro Leu Leu 
                85                  90                  95 

Pro Glu Leu Asn Ala Thr Leu Gly Ala Ser Arg Gln Lys Leu Leu Arg 
            100                 105                 110 

Asp Ser Gly Tyr Ser Gly Thr Asp Ala Thr Ser Asp Asn Asp Ala Val 
        115                 120                 125 

Asp Ser Phe Ser Ala Gly Leu Ser Ala Ser Tyr Glu Val Asp Phe Trp 
    130                 135                 140 

Gly Gly Arg Gln Ala Ala Tyr Arg Ser Ala Leu Glu Ser Leu Lys Ala 
145                 150                 155                 160 

Ser Glu Tyr Asp Arg Ala Thr Val Glu Leu Thr Leu Leu Ser Gly Val 
                165                 170                 175 

Ala Asn Ser Tyr Leu Gln Val Leu Ala Leu Arg Glu Gln Gln Arg Ile 
            180                 185                 190 

Ala Arg Leu Asn Leu Asp Asn Ala Glu His Val Leu Arg Leu Val Glu 
        195                 200                 205 

Thr Arg His Ala Ala Gly Ser Ala Thr Ala Leu Glu Val Ala Gln Gln 
    210                 215                 220 

Ser Ser Leu Val Ala Ser Gln Arg Lys Gln Leu Pro Leu Leu Glu Gln 
225                 230                 235                 240 

Gln Ala His Glu Ala Leu Ile Thr Leu Ala Thr Leu Ile Gly Glu Pro 
                245                 250                 255 

Val Gln Ala Leu Gln Val Ala Glu Arg Pro Phe Asp Ser Leu Arg Trp 
            260                 265                 270 

Pro Glu Thr Gly Ala Gly Leu Pro Ser Glu Leu Leu Ser Arg Arg Pro 
        275                 280                 285 

Asp Ile Ala Asn Ala Glu Ala Gln Leu Ala Ala Ala Gln Ala Asp Val 
    290                 295                 300 

Gln Val Ala Arg Ala Ala Leu Phe Pro Lys Leu Thr Leu Ser Ala Ser 
305                 310                 315                 320 

Leu Ser Ser Gly Ala Asn Arg Ala Ala Asp Thr Phe Arg Asn Pro Tyr 
                325                 330                 335 

Tyr Asn Leu Gly Ala Asn Leu Leu Ala Pro Ile Phe Asn His Gly Arg 
            340                 345                 350 

Leu Arg Ala Glu Arg Asp Arg Ser Leu Ala Arg Gln Glu Glu Leu Leu 
        355                 360                 365 

Glu Thr Tyr Arg Lys Ala Ile Leu Thr Ala Phe Ala Asp Thr Glu Arg 
    370                 375                 380 

Ser Leu Asn Ser Ile Asp Gly Leu Asp Arg Gln Leu His Trp Gln Gln 
385                 390                 395                 400 

Gln Glu Leu Glu Gln Ala Gln Arg Ala Phe Asp Leu Ser Asp Ser Arg 
                405                 410                 415 

Tyr Gln Ala Gly Ala Glu Thr Leu Leu Thr Val Leu Glu Thr Gln Arg 
            420                 425                 430 

Thr Leu Tyr Ala Ala Gln Asp Ala Ala Val Gln Leu Arg Leu Ala Arg 
        435                 440                 445 

Leu Gln Ala Ser Val Gly Leu Tyr Lys Ala Leu Gly Gly Gly Trp Gln 
    450                 455                 460 

Ser Asp Arg Gln Gly Leu Ala Arg Lys Asp 
465                 470 

 
           
             23  
             501  
             DNA  
             Pseudomonas aeruginosa  
           
            23 

ggtcgctcgc gggagaggat cggttggata acttggcatc gtgacgatga cgctttgatt     60 

gcaggacgat gaaggccgct tcgcgggatg cccggcgatg ctttccgttg gaactgtcgg    120 

ggtcgtcttg ccgtcgcctc gcgccgacga actacgaggt gccgggaagt gctatttcat    180 

ttctcccggt tttttatgaa atacgcatcg tagagttctg atatttgccc gctgggttat    240 

ttagtcgatt tgccgtgcca ggtgatgggg gttgtttata aagtattata actttttgat    300 

tatatattgt ttatcaatta gataggcgtg tgatggctaa atggctgcat gttttccagg    360 

ggttatctaa attgaatttt tcatgggggt tttcttagtc gttatatata aagtcagact    420 

cgccttttat ttaaaagctg ctatttctgg attacatggt gcggccgttc ggtcgctgct    480 

tgacaagagg aatgtcggaa a                                              501 

 
           
             24  
             501  
             DNA  
             Pseudomonas aeruginosa  
           
            24 

agcccatgaa aaaccgctaa tcctggcagt tcatcccact ctttcggatt agtaccattg     60 

aatggctttc cagactcatg ggaagcctaa aggagatata tgaaatgaaa gaactcaatg    120 

acattgaagt cacctgcgtt tcgggtggaa ctctttccgg catgatcgta ggcgccgtcg    180 

acggcgccgc gacgggcatg gcaatcggcg ggaaatgggg cggtgccggc ggcttcggct    240 

tcggcgctct ttcccagttg gtcggcctga tcgtgccaac cgcaatgggc gctattgccg    300 

ggggcacggt cggtctcttc accaatgcag agacggctgt cggttacttg ggccaatacc    360 

gggaaaactt cggtcccggt gatgtaggcc gcaccaccat ctaattagaa aagtcgcact    420 

ccggcacttc atgcgtttga actttcgcaa gggtgtcgga gtgtcatgca agtattattc    480 

gaatccagga tccagccacc a                                              501 

 
           
             25  
             501  
             DNA  
             Pseudomonas aeruginosa  
           
            25 

caacgtggta gtcaccgtca ccgagggctc ggtgaaggtc cgcagcgaag gctcgggcaa     60 

cgacagcagc ctgactcccg gcatgcaggc cagctactat ccgggcctgc tgcaaccgtt    120 

ggtcgaggcc gtggataccc gccagacgct agcctggcgc gagggccgcc tggtactcga    180 

cgacctgccc ctgtccaagg ccctgccgct gatcaaccgc tacctcgacg ctccgctggt    240 

cctgggcgac aggagcgctg cgaaactgcg cattggcggg atctacagca cccgcgacat    300 

ccgcagcctg gtcgacgccc tgccgaaagt cctgcccgtg gacctggaac atcgcgagga    360 

cggcagcatc cgcatcagca gccgttacgc ccagctctga acccaggtta aatttagccg    420 

ccctggcctc gtatatctgg cagtgcccag cctgccgatc cagcggcggc ggtctctcca    480 

cgcaccggcc ggattcccga a                                              501 

 
           
             26  
             501  
             DNA  
             Pseudomonas aeruginosa  
           
            26 

gctccgggt ggtcggcgac gaagcgctcg acggcgacga tcatcgacgc caggctgcct      60 

ttcatgtccg ccgcgccgcg cccgcagagc atgccctggt cgtcgatcag ggcgtcgaag    120 

ggttggtgct gccaggcctg cagcgggccg gtggggacca cgtcggtgtg cccggcgaag    180 

cacagcaccg ggccgtcgcc gccgcgccgt gcccagaagt tgtccacctc ctcgatgcgc    240 

atcggctcca gggcgaagcc ggcggcttcc aggcggcgca tcatcagggc ctggcagtcg    300 

gcgtcgagcg gcgtgacgga ggggcggcgg atcaactcgc aggcgagttc gagggtcggc    360 

gagagactcg gcgaagaggc ggtcatgggg agggcatcct gagcgggtcg agcggaaagg    420 

gggaatctta aagcataaac gtgggcgaag ggacgccgtt taggcgagcg gggccggccg    480 

tcccgacgcc tcgcccgacc t                                              501 

 
           
             27  
             920  
             PRT  
             Bradyrhizobium japonicum  
           
            27 

Met Arg Val Val Ala Ala Val Leu Leu Leu Val Ser Ala Leu His Ala 
 1               5                  10                  15 

Gly Leu Trp Gly Val Leu Arg Asp Lys Glu Pro Ala Pro Asp Phe Arg 
            20                  25                  30 

Gly Leu Leu Pro Ser Val Ser Tyr Ala Pro Phe Glu Gly Ser Ala His 
        35                  40                  45 

Pro Asp Ile Asp Asn Ile Pro Thr Val Glu Lys Ile Arg Ala Asp Leu 
    50                  55                  60 

Lys Thr Leu Ser Thr Met Thr Arg Ala Ile Arg Leu Tyr Ser Ser Thr 
65                  70                  75                  80 

Gly Gly Val Glu Leu Val Pro Ala Ile Ala Ala Glu Phe Gly Leu Lys 
                85                  90                  95 

Val Thr Val Gly Ala Trp Ile Asp Lys Asp Lys Asp Arg Asn Glu Arg 
            100                 105                 110 

Glu Ile Lys Ala Ala Ile Glu Leu Ala Arg Lys Asn Ser Asn Val Val 
        115                 120                 125 

Gly Val Val Val Gly Asn Glu Val Ile Tyr Arg Gly Glu Gln Lys Val 
    130                 135                 140 

Glu Asp Leu Ile Asp Met Ile Lys Lys Val Lys Gly Ser Val Arg Val 
145                 150                 155                 160 

Pro Val Thr Thr Gly Glu Ile Trp Asn Ile Trp Arg Asp Asn Pro Asp 
                165                 170                 175 

Leu Ala Ser Asn Val Asp Phe Ile Ala Ala His Val Leu Pro Tyr Trp 
            180                 185                 190 

Glu Asn Phe Arg Ser Asp Gln Ala Val Asp Gln Ala Val Asp Arg Tyr 
        195                 200                 205 

Asn Leu Leu Arg Asn Leu Phe Pro Gly Lys Arg Ile Val Ile Ala Glu 
    210                 215                 220 

Phe Gly Trp Pro Ser Gln Gly Tyr Asn Leu Arg Asn Ala Asp Pro Gly 
225                 230                 235                 240 

Pro Phe Gln Gln Ala Leu Thr Leu Arg Asn Phe Val Ser Arg Ala Glu 
                245                 250                 255 

Ala Ile Gly Met Glu Tyr Asn Ile Val Glu Ala Ile Asp Gln Pro Trp 
            260                 265                 270 

Lys Phe Phe Glu Gly Gly Val Gly Pro Tyr Trp Gly Ile Leu Asn Ala 
        275                 280                 285 

Ser Arg Glu Pro Lys Phe Ala Trp Thr Gly Pro Val Glu Asn Pro Asp 
    290                 295                 300 

Tyr Trp Lys Leu Met Thr Ile Ala Leu Leu Val Gly Val Leu Leu Ser 
305                 310                 315                 320 

Leu Pro Ile Leu Arg Leu Gln Gln Pro Thr Ala Lys Gln Ala Phe Leu 
                325                 330                 335 

Leu Ser Ala Thr Ala Asn Gly Val Gly Ala Trp Ala Ala Thr Val Phe 
            340                 345                 350 

Ala Phe Trp Asn Gly His Tyr Phe Ile Phe Gly Ser Ala Phe Ala Leu 
        355                 360                 365 

Thr Leu Gly Met Ile Leu Leu Val Pro Leu Val Leu Ile Ala Met Ala 
    370                 375                 380 

Arg Ile Asp Glu Ile Ala Ala Val Ala Phe Gly Arg Pro Pro Gln Arg 
385                 390                 395                 400 

Leu Leu Ala Lys Ser Lys Pro Val Glu Asn Val Pro Glu Asn Tyr Tyr 
                405                 410                 415 

Pro Lys Val Ser Ile His Ile Pro Ala Tyr Phe Glu Pro Val Glu Met 
            420                 425                 430 

Leu Lys Gln Thr Leu Asp Ala Leu Ser Arg Leu Asn Tyr Pro Asn Tyr 
        435                 440                 445 

Glu Cys Val Val Ile Ile Asn Asn Thr Pro Asp Pro Ala Phe Trp Gln 
    450                 455                 460 

Pro Ile Gln Asp His Cys Arg Ala Leu Gly Glu Arg Phe Lys Phe Ile 
465                 470                 475                 480 

Asn Ala Glu Lys Val Gln Gly Phe Lys Ala Gly Ala Leu Arg Ile Ala 
                485                 490                 495 

Met Asp Arg Thr Ala Val Asp Ala Glu Ile Ile Gly Ile Leu Asp Ala 
            500                 505                 510 

Asp Tyr Val Val Asp Pro Asp Trp Leu Lys Asp Leu Val Pro Ala Phe 
        515                 520                 525 

Ala Asp Pro Arg Val Gly Leu Val Gln Ala Pro Gln Glu His Arg Asp 
    530                 535                 540 

Gly Asp Leu Ser Ile Met His Tyr Ile Met Asn Gly Glu Tyr Ala Gly 
545                 550                 555                 560 

Phe Phe Asp Ile Gly Met Val Gln Arg Asn Glu Ala Asn Ala Ile Ile 
                565                 570                 575 

Val His Gly Thr Met Cys Leu Ile Arg Arg Ala Ala Met Asp Met Ala 
            580                 585                 590 

Gly Gly Trp Ser Ser Asp Thr Ile Cys Glu Asp Ser Asp Leu Gly Leu 
        595                 600                 605 

Ala Ile Gln Glu Leu Gly Trp Val Thr His Tyr Thr Asn His Arg Tyr 
    610                 615                 620 

Gly Gln Gly Leu Leu Pro Asp Thr Tyr Glu Ala Phe Lys Lys Gln Arg 
625                 630                 635                 640 

His Arg Trp Ala Tyr Gly Gly Leu Gln Ile Val Lys Lys His Trp Arg 
                645                 650                 655 

His Phe Leu Pro Gly Arg Ser Arg Leu Thr Pro Asp Gln Lys Arg Glu 
            660                 665                 670 

Tyr Gly Leu Gly Trp Leu Asn Trp Leu Gly Ala Glu Ser Leu Gly Val 
        675                 680                 685 

Val Val Ala Leu Leu Asn Leu Val Trp Val Pro Ile Val Ala Phe Ala 
    690                 695                 700 

Asp Ile Ala Ile Pro Asp Lys Ile Leu Thr Leu Pro Ile Ile Gly Ala 
705                 710                 715                 720 

Phe Val Val Ser Leu Ala His Phe Leu Ser Met Tyr Arg Ala Arg Val 
                725                 730                 735 

Ala Ile Lys Pro Gly Gln Met Leu Gly Ala Met Ile Ala Ala Met Ser 
            740                 745                 750 

Val Thr Val Asp Gly Val Ala Arg Gly Arg Ala Gly Thr Asp His Arg 
        755                 760                 765 

Ala His Arg Leu Arg Ala His Leu Gln Gly Arg Pro Val Gln Asp Val 
    770                 775                 780 

Asp Arg Val Pro Gly Val Leu Gly Gly Arg Asp Arg Arg Pro Ala Pro 
785                 790                 795                 800 

Asp Arg Arg Arg Arg Ala Asp Arg Leu Gln Gln Phe Pro Ala Asp His 
                805                 810                 815 

Arg Asp Leu His Leu Arg Arg Arg Ala Gly Ala Ala Lys Pro Ala Val 
            820                 825                 830 

Pro Gly Arg Gly Arg His Arg His Pro Arg Ala Gln Pro His Gln Leu 
        835                 840                 845 

Val Pro Val Leu Ala Arg Gln Arg Asp Pro His Arg Arg Ala Asp Trp 
    850                 855                 860 

Pro Ala Pro Gly Arg Pro Ala Asp Pro Arg Arg His Ala Ala Ser Arg 
865                 870                 875                 880 

Ala Glu Arg Gly Gln Ala Arg Gly Glu Leu Thr Ala Gly Trp Leu Leu 
                885                 890                 895 

Gly Ala Gly Glu Thr Ser Ala Pro Pro Ser His Arg Gln Arg Ser Glu 
            900                 905                 910 

Trp Ile Ala Gly Arg Gln Ser Gly 
        915                 920 

 
           
             28  
             654  
             PRT  
             Agrobacterium tumefaciens  
           
            28 

Met Tyr Phe Ser Ala Glu Gly Asp Val Gln Ser Val Leu Tyr Val Asn 
 1               5                  10                  15 

Leu Thr Ile Ala Ile Gly Ala Ile Leu Phe Ala Leu Leu Ala Asp Pro 
            20                  25                  30 

Arg Lys Met Val Asp Arg Leu Ala Phe Ser Ile Ile Met Leu Leu Ser 
        35                  40                  45 

Leu Gly Val Tyr Ile Val Trp Arg Ala Thr Asp Thr Leu Pro Pro Leu 
    50                  55                  60 

Glu Phe Ser Leu Glu Thr Leu Trp Cys Tyr Thr Tyr Phe Thr Phe Glu 
65                  70                  75                  80 

Leu Ile Ser Val Leu Tyr Ala Met Gly Ser Ile Leu Ile Leu Leu Arg 
                85                  90                  95 

Arg Thr Asp Trp Ser Ala Val Ala Asp Gln Gly Glu Ala Tyr Leu Ala 
            100                 105                 110 

Gly Asn Pro His Ala Pro Leu Val Asp Val Phe Ile Cys Thr Tyr Asn 
        115                 120                 125 

Glu Pro Leu Asn Val Leu Glu Lys Ser Ile Ile Ala Ala Gln Ala Met 
    130                 135                 140 

Asp Tyr Pro Arg Leu Arg Val Phe Val Cys Asp Asp Thr Arg Arg Ala 
145                 150                 155                 160 

Glu Val Arg Thr Tyr Cys Glu Ala Val Gly Val Asn Tyr Val Thr Arg 
                165                 170                 175 

Pro Asp Asn Lys His Ala Lys Ala Gly Asn Leu Asn Asn Ala Leu Leu 
            180                 185                 190 

His Thr Asn Ala Leu Glu Glu Val Ser Asp Phe Ile Met Val Leu Asp 
        195                 200                 205 

Ala Asp Phe Ala Pro Gln Ala Asn Phe Leu Arg Arg Val Thr Gly Leu 
    210                 215                 220 

Phe Ser Asp Pro Lys Val Ala Val Val Gln Thr Pro Gln Phe Tyr Phe 
225                 230                 235                 240 

Asn Ser Asp Pro Ile Gln His Asn Leu Gly Ile Asp Lys Ser Phe Val 
                245                 250                 255 

Asp Asp Gln Arg Val Phe Phe Asp Val Phe Gln Pro Ala Lys Asp Ala 
            260                 265                 270 

Val Gly Cys Ala Phe Cys Val Gly Thr Ser Phe Val Val Arg Arg Ala 
        275                 280                 285 

Ala Val Asn Gly Ile Gly Gly Phe Pro Ser Asp Ala Leu Ser Glu Asp 
    290                 295                 300 

Met Leu Leu Thr Tyr Arg Leu Met Glu Arg Gly Tyr Val Thr Arg Trp 
305                 310                 315                 320 

Leu Asn Glu Lys Leu Ser Val Gly Leu Ser Ala Glu Gly Val Pro Glu 
                325                 330                 335 

Tyr Ile Thr Gln Arg Thr Arg Trp Cys Leu Gly Thr Ile Gln Ile Gly 
            340                 345                 350 

Leu Leu Arg Thr Gly Pro Leu Trp Arg Gly Asn Phe Thr Leu Thr Gln 
        355                 360                 365 

Arg Leu His Tyr Leu His Gly Leu Phe Cys Trp Leu Ser Lys Pro Phe 
    370                 375                 380 

Ile Leu Cys Leu Leu Leu Ala Pro Ser Ile Tyr Trp Leu Thr Gly Val 
385                 390                 395                 400 

Ser Ala Leu Gln Ala Asp Glu Leu Met Phe Met Lys Leu Gly Leu Ser 
                405                 410                 415 

Ser Leu Ala Leu Phe Trp Thr Tyr Ser Thr Trp Ile Ser Gly Lys Arg 
            420                 425                 430 

Thr Leu Pro Leu Phe Thr Glu Val Thr His Ala Leu Thr Ala Val Pro 
        435                 440                 445 

Ile Thr Ile Thr Leu Phe Gln Ala Ile Arg Lys Pro Phe Gly Arg Pro 
    450                 455                 460 

Phe Lys Val Thr Glu Lys Gly Gly Asp Arg Ser Gln Val Arg Val His 
465                 470                 475                 480 

Leu Pro Thr Ala Ile Phe Phe Ala Phe Val Thr Leu Ser Ser Ala Val 
                485                 490                 495 

Ser Ile Val Leu Ala Val Tyr Gly Leu Asp Ala Pro Ser Glu Leu Ser 
            500                 505                 510 

Ser Arg Asp Cys Leu Asn Leu Ile Trp Ser Ala Val Ala Met Val Ile 
        515                 520                 525 

Ala Phe Thr Ser Phe Ile Cys Cys Ile Glu Leu Pro Arg Phe Gly Lys 
    530                 535                 540 

Glu Glu Met Ile Gly Val Asp Phe Arg Gly Gln Leu Arg Ser Ala Ser 
545                 550                 555                 560 

Ser Thr Arg Pro Val Arg Ile Thr Gly Leu Ser Thr Glu Asn Ile Thr 
                565                 570                 575 

Leu Ala Ala Val Pro Ser Ser Ser Asp Val Thr Asp Val Phe Val Pro 
            580                 585                 590 

Glu Ala Gly Trp Met Arg Ile Ser Pro Ala Glu His Ala Gln Asn Ser 
        595                 600                 605 

Gly Lys Phe Asp Ile His Pro Ser Asp Glu Gln Arg Arg Ser Ile Leu 
    610                 615                 620 

Arg Leu Leu Phe Arg Lys Ala Pro Glu Asn Val Ala Glu Gln Gly Asp 
625                 630                 635                 640 

Leu Met Lys Ser Met Arg Ile Leu Leu Ala Arg Ala Phe Gly 
                645                 650 

 
           
             29  
             2592  
             DNA  
             Pseudomonas putida  
             
               CDS  
               (1)...(2589)  
             
           
            29 

atg tct tca cgt aaa ttc ggc ctg aac ctg gta gtg gtg ctg gcc atc       48 
Met Ser Ser Arg Lys Phe Gly Leu Asn Leu Val Val Val Leu Ala Ile 
 1               5                   10                  15 

gcc gca ctg ttc acc ggg ttc tgg gca ctg atc aac cgc ccg gtc tcc       96 
Ala Ala Leu Phe Thr Gly Phe Trp Ala Leu Ile Asn Arg Pro Val Ser 
             20                  25                  30 

gcc ccc gcc tgg cca gaa cag atc tct ggc ttt tcg tat tcg ccg ttc      144 
Ala Pro Ala Trp Pro Glu Gln Ile Ser Gly Phe Ser Tyr Ser Pro Phe 
         35                  40                  45 

cgc ctg ggc gaa agc cca cag aag ggt cag tac ccc act gac gac gaa      192 
Arg Leu Gly Glu Ser Pro Gln Lys Gly Gln Tyr Pro Thr Asp Asp Glu 
     50                  55                  60 

atg cgc cag gac ctg gag caa ctg agc aaa ctg acc gac agc atc cgt      240 
Met Arg Gln Asp Leu Glu Gln Leu Ser Lys Leu Thr Asp Ser Ile Arg 
 65                  70                  75                  80 

atc tat acc gtg gaa ggc acc cag gcc gac gtc ccg cgc ctg gcc gag      288 
Ile Tyr Thr Val Glu Gly Thr Gln Ala Asp Val Pro Arg Leu Ala Glu 
                 85                  90                  95 

gag ttc ggc ctg cgg gtg acg ctg ggg ata tgg atc agc ccg gac ctg      336 
Glu Phe Gly Leu Arg Val Thr Leu Gly Ile Trp Ile Ser Pro Asp Leu 
            100                 105                 110 

gag cgc aac gag cgc gaa att gcc acg gcc atc cag ctg gcc aac acg      384 
Glu Arg Asn Glu Arg Glu Ile Ala Thr Ala Ile Gln Leu Ala Asn Thr 
        115                 120                 125 

tcg cgc agc gtg gtg cgg gtg gtg gtc ggc aac gag gcg ctg ttc cgt      432 
Ser Arg Ser Val Val Arg Val Val Val Gly Asn Glu Ala Leu Phe Arg 
    130                 135                 140 

gaa gaa gtc aca ccg gaa aac ctg atc aaa tac ctg gac cgc gta cgc      480 
Glu Glu Val Thr Pro Glu Asn Leu Ile Lys Tyr Leu Asp Arg Val Arg 
145                 150                 155                 160 

gca gcc gtg aag gtg ccc gtg acc acc agt gaa cag tgg cac atc tgg      528 
Ala Ala Val Lys Val Pro Val Thr Thr Ser Glu Gln Trp His Ile Trp 
                165                 170                 175 

aag gaa cat cct gag ctg gcc agg cac gtc gac ctg att gcc gcg cac      576 
Lys Glu His Pro Glu Leu Ala Arg His Val Asp Leu Ile Ala Ala His 
            180                 185                 190 

atc ctg ccc tac tgg gag ttc gtg ccg atg aag gat tcg gtc gag ttc      624 
Ile Leu Pro Tyr Trp Glu Phe Val Pro Met Lys Asp Ser Val Glu Phe 
        195                 200                 205 

gtc ctc gag cgc gcc cgt gaa ctg aag cac cag ttc ccg cgc aaa cct      672 
Val Leu Glu Arg Ala Arg Glu Leu Lys His Gln Phe Pro Arg Lys Pro 
    210                 215                 220 

ctg ctg ctg tcg gaa gtc ggc tgg ccg agc aac ggc cgc atg cgc ggt      720 
Leu Leu Leu Ser Glu Val Gly Trp Pro Ser Asn Gly Arg Met Arg Gly 
225                 230                 235                 240 

ggt gcc gat gcc aca cag gcc gac cag gcc atc tac ttg cgc acc ctg      768 
Gly Ala Asp Ala Thr Gln Ala Asp Gln Ala Ile Tyr Leu Arg Thr Leu 
                245                 250                 255 

gtc aat acc ctc aac cgc cgt ggc tac aac tac ttt gtc att gaa gcc      816 
Val Asn Thr Leu Asn Arg Arg Gly Tyr Asn Tyr Phe Val Ile Glu Ala 
            260                 265                 270 

tat gac caa ccc tgg aag gcc agc gac gaa gga tcg gta ggc gcc tac      864 
Tyr Asp Gln Pro Trp Lys Ala Ser Asp Glu Gly Ser Val Gly Ala Tyr 
        275                 280                 285 

tgg ggc gtc tac aac gcc gag cgc cag cag aag ttc aac ttc gac ggc      912 
Trp Gly Val Tyr Asn Ala Glu Arg Gln Gln Lys Phe Asn Phe Asp Gly 
    290                 295                 300 

ccc gtg gtg gcg atc ccg cag tgg cgg gcc ctg gca gtg gcg tcg gtg      960 
Pro Val Val Ala Ile Pro Gln Trp Arg Ala Leu Ala Val Ala Ser Val 
305                 310                 315                 320 

gtg ctg gca atg atc gcc ttg atg gtg ctg ttc atc gat ggc tcg gcc     1008 
Val Leu Ala Met Ile Ala Leu Met Val Leu Phe Ile Asp Gly Ser Ala 
                325                 330                 335 

ctg cgc cag cgt ggc cgt acc ttc ctg acg ttc atc acc ttc ctg tgc     1056 
Leu Arg Gln Arg Gly Arg Thr Phe Leu Thr Phe Ile Thr Phe Leu Cys 
            340                 345                 350 

ggg tcg gtg ctg gtg tgg atc gcc tac gac tac agc cag caa tac agc     1104 
Gly Ser Val Leu Val Trp Ile Ala Tyr Asp Tyr Ser Gln Gln Tyr Ser 
        355                 360                 365 

acc tgg ttc agc ctg acc gtg ggc gtg ctg ctg gcc ctc ggc gcg ctg     1152 
Thr Trp Phe Ser Leu Thr Val Gly Val Leu Leu Ala Leu Gly Ala Leu 
    370                 375                 380 

ggt gtg ttc atc gtg ctg ctc acc gag gcc cac gaa ctg gcc gag gcg     1200 
Gly Val Phe Ile Val Leu Leu Thr Glu Ala His Glu Leu Ala Glu Ala 
385                 390                 395                 400 

gtc tgg ata cac aag cgc cgc cgc gag ttc ctg ccc gtg cag gcc gac     1248 
Val Trp Ile His Lys Arg Arg Arg Glu Phe Leu Pro Val Gln Ala Asp 
                405                 410                 415 

act gcc tac cgg ccc aag gtg tcg gtg cat gtg ccg tgc tac aac gag     1296 
Thr Ala Tyr Arg Pro Lys Val Ser Val His Val Pro Cys Tyr Asn Glu 
            420                 425                 430 

cca cct gag atg gtg aaa cag acc ctg gac gcc ctg gcc gcc ctg gac     1344 
Pro Pro Glu Met Val Lys Gln Thr Leu Asp Ala Leu Ala Ala Leu Asp 
        435                 440                 445 

tac ccc gac tac gaa gtg ctg gtg atc gac aac aac acc aag gac ccg     1392 
Tyr Pro Asp Tyr Glu Val Leu Val Ile Asp Asn Asn Thr Lys Asp Pro 
    450                 455                 460 

gcc gtg tgg gag ccg ctc aag gcc cac tgc gaa aag ctt ggc gag cgc     1440 
Ala Val Trp Glu Pro Leu Lys Ala His Cys Glu Lys Leu Gly Glu Arg 
465                 470                 475                 480 

ttc aag ttc ttc cac gtc gcg cca ctg gcc ggc ttc aag ggt ggc gcg     1488 
Phe Lys Phe Phe His Val Ala Pro Leu Ala Gly Phe Lys Gly Gly Ala 
                485                 490                 495 

ctg aat tac ctg atc ccg cac acg gca aag gac gcc gaa gtg atc gcg     1536 
Leu Asn Tyr Leu Ile Pro His Thr Ala Lys Asp Ala Glu Val Ile Ala 
            500                 505                 510 

gta atc gac tcg gac tac tgc gtc gac cgc aac tgg ctc aag cac atg     1584 
Val Ile Asp Ser Asp Tyr Cys Val Asp Arg Asn Trp Leu Lys His Met 
        515                 520                 525 

gtg ccg cac ttc gcc gac ccg aaa att gcc gtg gtg cag tca ccg cag     1632 
Val Pro His Phe Ala Asp Pro Lys Ile Ala Val Val Gln Ser Pro Gln 
    530                 535                 540 

gat tac cgt gac cag cac gaa agc gcc ttc aag aag ctg tgc tac agc     1680 
Asp Tyr Arg Asp Gln His Glu Ser Ala Phe Lys Lys Leu Cys Tyr Ser 
545                 550                 555                 560 

gaa tac aag ggc ttc ttc cac atc ggt atg gtc acc cgc aac gac cgt     1728 
Glu Tyr Lys Gly Phe Phe His Ile Gly Met Val Thr Arg Asn Asp Arg 
                565                 570                 575 

gac gcg atc atc cag cac ggc acc atg acc atg acc cgg cgc agt gtg     1776 
Asp Ala Ile Ile Gln His Gly Thr Met Thr Met Thr Arg Arg Ser Val 
            580                 585                 590 

ctg gaa gaa ctg ggc tgg gcc gag tgg tgc atc tgc gag gac gcc gaa     1824 
Leu Glu Glu Leu Gly Trp Ala Glu Trp Cys Ile Cys Glu Asp Ala Glu 
        595                 600                 605 

ctg ggc ctg cgc gtg ttc gag aaa ggc ctg tcc gcc gcc tac gcc cac     1872 
Leu Gly Leu Arg Val Phe Glu Lys Gly Leu Ser Ala Ala Tyr Ala His 
    610                 615                 620 

aac agc tac ggc aag ggc ctg atg ccc gac acc ttc atc gac ttc aag     1920 
Asn Ser Tyr Gly Lys Gly Leu Met Pro Asp Thr Phe Ile Asp Phe Lys 
625                 630                 635                 640 

aag caa cgc ttc cgc tgg gcc tac ggc gcc atc cag atc atc aag cac     1968 
Lys Gln Arg Phe Arg Trp Ala Tyr Gly Ala Ile Gln Ile Ile Lys His 
                645                 650                 655 

cac gcc ggc gcg ctg ctg cgc ggc aaa ggc agc cag ctg acc cgt ggc     2016 
His Ala Gly Ala Leu Leu Arg Gly Lys Gly Ser Gln Leu Thr Arg Gly 
            660                 665                 670 

cag cgc tac cac ttc ctg gcc ggc tgg cta ccg tgg atc gcc gat ggc     2064 
Gln Arg Tyr His Phe Leu Ala Gly Trp Leu Pro Trp Ile Ala Asp Gly 
        675                 680                 685 

atg aac atc ttc ttc acc atc ggc gcg ctg ttg tgg tcg gcg gcg atg     2112 
Met Asn Ile Phe Phe Thr Ile Gly Ala Leu Leu Trp Ser Ala Ala Met 
    690                 695                 700 

atc atc gtg ccg cat cgg gtc gat ccg ccc ctg atg atc ttc gcc atc     2160 
Ile Ile Val Pro His Arg Val Asp Pro Pro Leu Met Ile Phe Ala Ile 
705                 710                 715                 720 

ccg ccg ctg gcg ctg ttc ttc ttc aag gtc ggc aag atc atc ttc ctg     2208 
Pro Pro Leu Ala Leu Phe Phe Phe Lys Val Gly Lys Ile Ile Phe Leu 
                725                 730                 735 

tac cgc cga gcg gtg ggg gtg aac ctc aag gat gcc ttc gca gct gcg     2256 
Tyr Arg Arg Ala Val Gly Val Asn Leu Lys Asp Ala Phe Ala Ala Ala 
            740                 745                 750 

ctg gcc ggg ctg gca ctg tcg cac acc atc gcc aag gcg gta ctg tat     2304 
Leu Ala Gly Leu Ala Leu Ser His Thr Ile Ala Lys Ala Val Leu Tyr 
        755                 760                 765 

ggt ttc ttc acc agc agc atg ccg ttc ttc cgc acg ccg aag aac gct     2352 
Gly Phe Phe Thr Ser Ser Met Pro Phe Phe Arg Thr Pro Lys Asn Ala 
    770                 775                 780 

gac agc cat ggg ttg ctg gtg gcg att tcc gaa gcc cgt gaa gag ctg     2400 
Asp Ser His Gly Leu Leu Val Ala Ile Ser Glu Ala Arg Glu Glu Leu 
785                 790                 795                 800 

ttc atc atg gtg ctg ctg tgg ggc gcg gcg ttg ggt atc tac ctg gtg     2448 
Phe Ile Met Val Leu Leu Trp Gly Ala Ala Leu Gly Ile Tyr Leu Val 
                805                 810                 815 

cag ggg ctg ccg agt tcg gac atg cgc ttc tgg gtg gcg atg ttg ctg     2496 
Gln Gly Leu Pro Ser Ser Asp Met Arg Phe Trp Val Ala Met Leu Leu 
            820                 825                 830 

gtg cag tcg ttg cct tat gtg gca gcg ctg gtg atg gcg ttc ctg tcg     2544 
Val Gln Ser Leu Pro Tyr Val Ala Ala Leu Val Met Ala Phe Leu Ser 
        835                 840                 845 

tcg ctg ccc aag ccc gca gaa aag gct gcc caa gcg cag cag gct         2589 
Ser Leu Pro Lys Pro Ala Glu Lys Ala Ala Gln Ala Gln Gln Ala 
    850                 855                 860 

tga                                                                 2592 

 
           
             30  
             863  
             PRT  
             Pseudomonas putida  
           
            30 

Met Ser Ser Arg Lys Phe Gly Leu Asn Leu Val Val Val Leu Ala Ile 
 1               5                  10                  15 

Ala Ala Leu Phe Thr Gly Phe Trp Ala Leu Ile Asn Arg Pro Val Ser 
            20                  25                  30 

Ala Pro Ala Trp Pro Glu Gln Ile Ser Gly Phe Ser Tyr Ser Pro Phe 
        35                  40                  45 

Arg Leu Gly Glu Ser Pro Gln Lys Gly Gln Tyr Pro Thr Asp Asp Glu 
    50                  55                  60 

Met Arg Gln Asp Leu Glu Gln Leu Ser Lys Leu Thr Asp Ser Ile Arg 
65                  70                  75                  80 

Ile Tyr Thr Val Glu Gly Thr Gln Ala Asp Val Pro Arg Leu Ala Glu 
                85                  90                  95 

Glu Phe Gly Leu Arg Val Thr Leu Gly Ile Trp Ile Ser Pro Asp Leu 
            100                 105                 110 

Glu Arg Asn Glu Arg Glu Ile Ala Thr Ala Ile Gln Leu Ala Asn Thr 
        115                 120                 125 

Ser Arg Ser Val Val Arg Val Val Val Gly Asn Glu Ala Leu Phe Arg 
    130                 135                 140 

Glu Glu Val Thr Pro Glu Asn Leu Ile Lys Tyr Leu Asp Arg Val Arg 
145                 150                 155                 160 

Ala Ala Val Lys Val Pro Val Thr Thr Ser Glu Gln Trp His Ile Trp 
                165                 170                 175 

Lys Glu His Pro Glu Leu Ala Arg His Val Asp Leu Ile Ala Ala His 
            180                 185                 190 

Ile Leu Pro Tyr Trp Glu Phe Val Pro Met Lys Asp Ser Val Glu Phe 
        195                 200                 205 

Val Leu Glu Arg Ala Arg Glu Leu Lys His Gln Phe Pro Arg Lys Pro 
    210                 215                 220 

Leu Leu Leu Ser Glu Val Gly Trp Pro Ser Asn Gly Arg Met Arg Gly 
225                 230                 235                 240 

Gly Ala Asp Ala Thr Gln Ala Asp Gln Ala Ile Tyr Leu Arg Thr Leu 
                245                 250                 255 

Val Asn Thr Leu Asn Arg Arg Gly Tyr Asn Tyr Phe Val Ile Glu Ala 
            260                 265                 270 

Tyr Asp Gln Pro Trp Lys Ala Ser Asp Glu Gly Ser Val Gly Ala Tyr 
        275                 280                 285 

Trp Gly Val Tyr Asn Ala Glu Arg Gln Gln Lys Phe Asn Phe Asp Gly 
    290                 295                 300 

Pro Val Val Ala Ile Pro Gln Trp Arg Ala Leu Ala Val Ala Ser Val 
305                 310                 315                 320 

Val Leu Ala Met Ile Ala Leu Met Val Leu Phe Ile Asp Gly Ser Ala 
                325                 330                 335 

Leu Arg Gln Arg Gly Arg Thr Phe Leu Thr Phe Ile Thr Phe Leu Cys 
            340                 345                 350 

Gly Ser Val Leu Val Trp Ile Ala Tyr Asp Tyr Ser Gln Gln Tyr Ser 
        355                 360                 365 

Thr Trp Phe Ser Leu Thr Val Gly Val Leu Leu Ala Leu Gly Ala Leu 
    370                 375                 380 

Gly Val Phe Ile Val Leu Leu Thr Glu Ala His Glu Leu Ala Glu Ala 
385                 390                 395                 400 

Val Trp Ile His Lys Arg Arg Arg Glu Phe Leu Pro Val Gln Ala Asp 
                405                 410                 415 

Thr Ala Tyr Arg Pro Lys Val Ser Val His Val Pro Cys Tyr Asn Glu 
            420                 425                 430 

Pro Pro Glu Met Val Lys Gln Thr Leu Asp Ala Leu Ala Ala Leu Asp 
        435                 440                 445 

Tyr Pro Asp Tyr Glu Val Leu Val Ile Asp Asn Asn Thr Lys Asp Pro 
    450                 455                 460 

Ala Val Trp Glu Pro Leu Lys Ala His Cys Glu Lys Leu Gly Glu Arg 
465                 470                 475                 480 

Phe Lys Phe Phe His Val Ala Pro Leu Ala Gly Phe Lys Gly Gly Ala 
                485                 490                 495 

Leu Asn Tyr Leu Ile Pro His Thr Ala Lys Asp Ala Glu Val Ile Ala 
            500                 505                 510 

Val Ile Asp Ser Asp Tyr Cys Val Asp Arg Asn Trp Leu Lys His Met 
        515                 520                 525 

Val Pro His Phe Ala Asp Pro Lys Ile Ala Val Val Gln Ser Pro Gln 
    530                 535                 540 

Asp Tyr Arg Asp Gln His Glu Ser Ala Phe Lys Lys Leu Cys Tyr Ser 
545                 550                 555                 560 

Glu Tyr Lys Gly Phe Phe His Ile Gly Met Val Thr Arg Asn Asp Arg 
                565                 570                 575 

Asp Ala Ile Ile Gln His Gly Thr Met Thr Met Thr Arg Arg Ser Val 
            580                 585                 590 

Leu Glu Glu Leu Gly Trp Ala Glu Trp Cys Ile Cys Glu Asp Ala Glu 
        595                 600                 605 

Leu Gly Leu Arg Val Phe Glu Lys Gly Leu Ser Ala Ala Tyr Ala His 
    610                 615                 620 

Asn Ser Tyr Gly Lys Gly Leu Met Pro Asp Thr Phe Ile Asp Phe Lys 
625                 630                 635                 640 

Lys Gln Arg Phe Arg Trp Ala Tyr Gly Ala Ile Gln Ile Ile Lys His 
                645                 650                 655 

His Ala Gly Ala Leu Leu Arg Gly Lys Gly Ser Gln Leu Thr Arg Gly 
            660                 665                 670 

Gln Arg Tyr His Phe Leu Ala Gly Trp Leu Pro Trp Ile Ala Asp Gly 
        675                 680                 685 

Met Asn Ile Phe Phe Thr Ile Gly Ala Leu Leu Trp Ser Ala Ala Met 
    690                 695                 700 

Ile Ile Val Pro His Arg Val Asp Pro Pro Leu Met Ile Phe Ala Ile 
705                 710                 715                 720 

Pro Pro Leu Ala Leu Phe Phe Phe Lys Val Gly Lys Ile Ile Phe Leu 
                725                 730                 735 

Tyr Arg Arg Ala Val Gly Val Asn Leu Lys Asp Ala Phe Ala Ala Ala 
            740                 745                 750 

Leu Ala Gly Leu Ala Leu Ser His Thr Ile Ala Lys Ala Val Leu Tyr 
        755                 760                 765 

Gly Phe Phe Thr Ser Ser Met Pro Phe Phe Arg Thr Pro Lys Asn Ala 
    770                 775                 780 

Asp Ser His Gly Leu Leu Val Ala Ile Ser Glu Ala Arg Glu Glu Leu 
785                 790                 795                 800 

Phe Ile Met Val Leu Leu Trp Gly Ala Ala Leu Gly Ile Tyr Leu Val 
                805                 810                 815 

Gln Gly Leu Pro Ser Ser Asp Met Arg Phe Trp Val Ala Met Leu Leu 
            820                 825                 830 

Val Gln Ser Leu Pro Tyr Val Ala Ala Leu Val Met Ala Phe Leu Ser 
        835                 840                 845 

Ser Leu Pro Lys Pro Ala Glu Lys Ala Ala Gln Ala Gln Gln Ala 
    850                 855                 860 

 
           
             31  
             2529  
             DNA  
             Pseudomonas syringae  
             
               CDS  
               (1)...(2526)  
             
           
            31 

atg tcg ata tac cgc atg gag cac agt tta gac atg aat aaa aaa ata       48 
Met Ser Ile Tyr Arg Met Glu His Ser Leu Asp Met Asn Lys Lys Ile 
 1               5                   10                  15 

tca gac gct cca atc tgg ccg gtc aac tca ttc aaa tcc gtc gtg acc       96 
Ser Asp Ala Pro Ile Trp Pro Val Asn Ser Phe Lys Ser Val Val Thr 
             20                  25                  30 

aaa gtc ccg gac tgg cct gac agc atc tcg ggc ctt gcc tat aac ccc      144 
Lys Val Pro Asp Trp Pro Asp Ser Ile Ser Gly Leu Ala Tyr Asn Pro 
         35                  40                  45 

ttt cgt ccc gga caa agt ccc tac aag cac atc tat ccg acc cgc gag      192 
Phe Arg Pro Gly Gln Ser Pro Tyr Lys His Ile Tyr Pro Thr Arg Glu 
     50                  55                  60 

caa atc aaa gaa gac ttg ctg ctg atc cgc ccg ttg act cga cat gta      240 
Gln Ile Lys Glu Asp Leu Leu Leu Ile Arg Pro Leu Thr Arg His Val 
 65                  70                  75                  80 

aga acc tac tcg gtc gag cag acg ctg gcc tgt att ccc gaa ata gcc      288 
Arg Thr Tyr Ser Val Glu Gln Thr Leu Ala Cys Ile Pro Glu Ile Ala 
                 85                  90                  95 

gaa gaa ctc ggc atg agt gtc aca ctc ggc ata tgg ata ggc tgg gac      336 
Glu Glu Leu Gly Met Ser Val Thr Leu Gly Ile Trp Ile Gly Trp Asp 
            100                 105                 110 

gaa aaa cgc aat gat cgg gaa ctg atc gag ggc gtg aag ctt gcc aat      384 
Glu Lys Arg Asn Asp Arg Glu Leu Ile Glu Gly Val Lys Leu Ala Asn 
        115                 120                 125 

cag tat ccc agc gtc cgg cgt ctg atc atc gga aat gaa aca tta ctg      432 
Gln Tyr Pro Ser Val Arg Arg Leu Ile Ile Gly Asn Glu Thr Leu Leu 
    130                 135                 140 

cgc aat gac gtc acc gtc agc caa ctg atc gat tac atg caa acg gca      480 
Arg Asn Asp Val Thr Val Ser Gln Leu Ile Asp Tyr Met Gln Thr Ala 
145                 150                 155                 160 

cga caa ggt gtc aac gtt ccg att tca acc tca gag gga tgg caa cag      528 
Arg Gln Gly Val Asn Val Pro Ile Ser Thr Ser Glu Gly Trp Gln Gln 
                165                 170                 175 

tgg cac gat acg ccg gaa ctg gct gat cac gca gac ttc atc gcg gcg      576 
Trp His Asp Thr Pro Glu Leu Ala Asp His Ala Asp Phe Ile Ala Ala 
            180                 185                 190 

cat gtc ttg cca ttc agg gag ttc gtt cca gtc acc cag gca ggc tct      624 
His Val Leu Pro Phe Arg Glu Phe Val Pro Val Thr Gln Ala Gly Ser 
        195                 200                 205 

gca gtt ctc gca cgg gcg aac gaa ttg agg ctg atg ttt ccc gaa aaa      672 
Ala Val Leu Ala Arg Ala Asn Glu Leu Arg Leu Met Phe Pro Glu Lys 
    210                 215                 220 

ccg ctg ata ctt tcc gag att ggc tgg cca gac aaa ggc aac ttc aga      720 
Pro Leu Ile Leu Ser Glu Ile Gly Trp Pro Asp Lys Gly Asn Phe Arg 
225                 230                 235                 240 

aga cgc acc acc gcc tac gtc gcc gaa cag tca att tac ctg cgc agc      768 
Arg Arg Thr Thr Ala Tyr Val Ala Glu Gln Ser Ile Tyr Leu Arg Ser 
                245                 250                 255 

cag ctc gcg ctg ttg aac cag agt ggc ctc gac tac ttt gtc agg gag      816 
Gln Leu Ala Leu Leu Asn Gln Ser Gly Leu Asp Tyr Phe Val Arg Glu 
            260                 265                 270 

gca ttt gat caa caa tgg aaa act gag gaa ggg ttg ccg ggg cct cac      864 
Ala Phe Asp Gln Gln Trp Lys Thr Glu Glu Gly Leu Pro Gly Pro His 
        275                 280                 285 

tgg ggc ctg ttc gat gcc cag cga aag ata aag tta cca ctg caa ggc      912 
Trp Gly Leu Phe Asp Ala Gln Arg Lys Ile Lys Leu Pro Leu Gln Gly 
    290                 295                 300 

cca gtg aaa ata cgg gcc agc tgg cga tca gaa gtt ccg aga ttg gtc      960 
Pro Val Lys Ile Arg Ala Ser Trp Arg Ser Glu Val Pro Arg Leu Val 
305                 310                 315                 320 

gcc gat tgg cag ccc gac aac tgg cga aca acc gta ttg att ttt gct     1008 
Ala Asp Trp Gln Pro Asp Asn Trp Arg Thr Thr Val Leu Ile Phe Ala 
                325                 330                 335 

gcg ttg tac aca tta ttg gta ggc gtt ggc ata agt tac gca cag ccc     1056 
Ala Leu Tyr Thr Leu Leu Val Gly Val Gly Ile Ser Tyr Ala Gln Pro 
            340                 345                 350 

tta tcg atg tgg gtg gct ttg ccc atc gcc ttg gtg tgg gtg acc agc     1104 
Leu Ser Met Trp Val Ala Leu Pro Ile Ala Leu Val Trp Val Thr Ser 
        355                 360                 365 

tta ctg atc ggc acg ggg ata cag ggt tac gag ttc ctc gaa tca tgc     1152 
Leu Leu Ile Gly Thr Gly Ile Gln Gly Tyr Glu Phe Leu Glu Ser Cys 
    370                 375                 380 

tgg gga ccg gag aaa ccg cga tct ttt cct ccg tta aga gct tac ccg     1200 
Trp Gly Pro Glu Lys Pro Arg Ser Phe Pro Pro Leu Arg Ala Tyr Pro 
385                 390                 395                 400 

ggg ccg tta ccc aaa gtg tcc ata cac gta ccg tgc tac aac gaa cct     1248 
Gly Pro Leu Pro Lys Val Ser Ile His Val Pro Cys Tyr Asn Glu Pro 
                405                 410                 415 

ccc gac atg gtg aag ctg acg ctc gac gca tta caa cgc ctg gac tat     1296 
Pro Asp Met Val Lys Leu Thr Leu Asp Ala Leu Gln Arg Leu Asp Tyr 
            420                 425                 430 

ccg aac ttt gag gtt ctg atc atc gac aac aac act caa gac ccg gaa     1344 
Pro Asn Phe Glu Val Leu Ile Ile Asp Asn Asn Thr Gln Asp Pro Glu 
        435                 440                 445 

gtc tgg gag ccc att gag cag tac tgc agg caa ctg gga cct cgc ttc     1392 
Val Trp Glu Pro Ile Glu Gln Tyr Cys Arg Gln Leu Gly Pro Arg Phe 
    450                 455                 460 

cgg ctc ttt cat gtc aat cca ctt agc ggg ttc aag tcg ggc gca ctg     1440 
Arg Leu Phe His Val Asn Pro Leu Ser Gly Phe Lys Ser Gly Ala Leu 
465                 470                 475                 480 

aac tac ctg ctg gac tac acc gcc aag gat gcc gaa ata gta gcg gcg     1488 
Asn Tyr Leu Leu Asp Tyr Thr Ala Lys Asp Ala Glu Ile Val Ala Ala 
                485                 490                 495 

atc gat gct gat tat tgc gtg cac cgg cat tgg ctc aag cat atg gcc     1536 
Ile Asp Ala Asp Tyr Cys Val His Arg His Trp Leu Lys His Met Ala 
            500                 505                 510 

ccc tat ttt gcg tgc ccg gat ata gcg gtt atc caa gta ccg caa gac     1584 
Pro Tyr Phe Ala Cys Pro Asp Ile Ala Val Ile Gln Val Pro Gln Asp 
        515                 520                 525 

tac cgt gat ggc gac gac agc ctg ttc aaa cgt tgc tgc cag gcc gag     1632 
Tyr Arg Asp Gly Asp Asp Ser Leu Phe Lys Arg Cys Cys Gln Ala Glu 
    530                 535                 540 

tat cgc gtt ttt ttc aat att ggc atg gtc atc cgc aac gac cac gac     1680 
Tyr Arg Val Phe Phe Asn Ile Gly Met Val Ile Arg Asn Asp His Asp 
545                 550                 555                 560 

gca atc att cag cac ggc acc atg acc ctg att cgc aat tcg gtg ttg     1728 
Ala Ile Ile Gln His Gly Thr Met Thr Leu Ile Arg Asn Ser Val Leu 
                565                 570                 575 

cag cga ctg cgc tgg gca gaa tgg agc atc tgc gaa gat gcc gag ctc     1776 
Gln Arg Leu Arg Trp Ala Glu Trp Ser Ile Cys Glu Asp Ala Glu Leu 
            580                 585                 590 

gga ctg cgg ata ctg gag aac ggt ttt tcc acc ggc tat gtc gcc atc     1824 
Gly Leu Arg Ile Leu Glu Asn Gly Phe Ser Thr Gly Tyr Val Ala Ile 
        595                 600                 605 

agc tat ggc aag gga ctg atc ccg gat aca ttc atg gac ttc aag aaa     1872 
Ser Tyr Gly Lys Gly Leu Ile Pro Asp Thr Phe Met Asp Phe Lys Lys 
    610                 615                 620 

caa cgg tat cgc tgg gct tac ggt gtc atc cag ata ctc aaa cga cat     1920 
Gln Arg Tyr Arg Trp Ala Tyr Gly Val Ile Gln Ile Leu Lys Arg His 
625                 630                 635                 640 

act gga agc ctg atc gca ggt acg tgc gag gcc ttg acg cca ata cag     1968 
Thr Gly Ser Leu Ile Ala Gly Thr Cys Glu Ala Leu Thr Pro Ile Gln 
                645                 650                 655 

cgc tat cac ttc att gcc ggc tgg atg cct tgg att gca ggg gga ata     2016 
Arg Tyr His Phe Ile Ala Gly Trp Met Pro Trp Ile Ala Gly Gly Ile 
            660                 665                 670 

aat tac ttt ctg gct atc gct gtg ctt ctc tgg tca atg gca atg atc     2064 
Asn Tyr Phe Leu Ala Ile Ala Val Leu Leu Trp Ser Met Ala Met Ile 
        675                 680                 685 

att caa ccc gac aca ctc gaa cct gtg ccg tgg ata ttt tca tcc tca     2112 
Ile Gln Pro Asp Thr Leu Glu Pro Val Pro Trp Ile Phe Ser Ser Ser 
    690                 695                 700 

tta ctg ttg atg ttt gtt ctg ggc gtt tgc aaa gcg atc agc ctt tat     2160 
Leu Leu Leu Met Phe Val Leu Gly Val Cys Lys Ala Ile Ser Leu Tyr 
705                 710                 715                 720 

caa cga ttg gcc agc acc gac atc aaa gac gcc ttc gca gcc ata att     2208 
Gln Arg Leu Ala Ser Thr Asp Ile Lys Asp Ala Phe Ala Ala Ile Ile 
                725                 730                 735 

gcg agc atg gcg ctg tac tcg gtt gta ggc aag gcc gtg ctt tca tcg     2256 
Ala Ser Met Ala Leu Tyr Ser Val Val Gly Lys Ala Val Leu Ser Ser 
            740                 745                 750 

gca ttc acc tca gga tta ccg ttc ttt cgc act ccc aag cag acc tct     2304 
Ala Phe Thr Ser Gly Leu Pro Phe Phe Arg Thr Pro Lys Gln Thr Ser 
        755                 760                 765 

ggc agc ggg ctc ggc aag gcc ctg ctg gac gtc cgg gaa gat ctg tac     2352 
Gly Ser Gly Leu Gly Lys Ala Leu Leu Asp Val Arg Glu Asp Leu Tyr 
    770                 775                 780 

atg gcc gtg gtc tgg tgg gtc atg acg gta tcg ctg tgc ttc cga aaa     2400 
Met Ala Val Val Trp Trp Val Met Thr Val Ser Leu Cys Phe Arg Lys 
785                 790                 795                 800 

gaa gct atc ggt ccg gac ctt gga ttc tgg gtg gcg ata atg ttc gcc     2448 
Glu Ala Ile Gly Pro Asp Leu Gly Phe Trp Val Ala Ile Met Phe Ala 
                805                 810                 815 

cag tca ttg cct tac gta gcc gcc atg atc atg gca ata ctg tcg gct     2496 
Gln Ser Leu Pro Tyr Val Ala Ala Met Ile Met Ala Ile Leu Ser Ala 
            820                 825                 830 

ctc gca aac cgc cct tca cgc tcc aca acc tga                         2529 
Leu Ala Asn Arg Pro Ser Arg Ser Thr Thr 
        835                 840 

 
           
             32  
             842  
             PRT  
             Pseudomonas syringae  
           
            32 

Met Ser Ile Tyr Arg Met Glu His Ser Leu Asp Met Asn Lys Lys Ile 
 1               5                  10                  15 

Ser Asp Ala Pro Ile Trp Pro Val Asn Ser Phe Lys Ser Val Val Thr 
            20                  25                  30 

Lys Val Pro Asp Trp Pro Asp Ser Ile Ser Gly Leu Ala Tyr Asn Pro 
        35                  40                  45 

Phe Arg Pro Gly Gln Ser Pro Tyr Lys His Ile Tyr Pro Thr Arg Glu 
    50                  55                  60 

Gln Ile Lys Glu Asp Leu Leu Leu Ile Arg Pro Leu Thr Arg His Val 
65                  70                  75                  80 

Arg Thr Tyr Ser Val Glu Gln Thr Leu Ala Cys Ile Pro Glu Ile Ala 
                85                  90                  95 

Glu Glu Leu Gly Met Ser Val Thr Leu Gly Ile Trp Ile Gly Trp Asp 
            100                 105                 110 

Glu Lys Arg Asn Asp Arg Glu Leu Ile Glu Gly Val Lys Leu Ala Asn 
        115                 120                 125 

Gln Tyr Pro Ser Val Arg Arg Leu Ile Ile Gly Asn Glu Thr Leu Leu 
    130                 135                 140 

Arg Asn Asp Val Thr Val Ser Gln Leu Ile Asp Tyr Met Gln Thr Ala 
145                 150                 155                 160 

Arg Gln Gly Val Asn Val Pro Ile Ser Thr Ser Glu Gly Trp Gln Gln 
                165                 170                 175 

Trp His Asp Thr Pro Glu Leu Ala Asp His Ala Asp Phe Ile Ala Ala 
            180                 185                 190 

His Val Leu Pro Phe Arg Glu Phe Val Pro Val Thr Gln Ala Gly Ser 
        195                 200                 205 

Ala Val Leu Ala Arg Ala Asn Glu Leu Arg Leu Met Phe Pro Glu Lys 
    210                 215                 220 

Pro Leu Ile Leu Ser Glu Ile Gly Trp Pro Asp Lys Gly Asn Phe Arg 
225                 230                 235                 240 

Arg Arg Thr Thr Ala Tyr Val Ala Glu Gln Ser Ile Tyr Leu Arg Ser 
                245                 250                 255 

Gln Leu Ala Leu Leu Asn Gln Ser Gly Leu Asp Tyr Phe Val Arg Glu 
            260                 265                 270 

Ala Phe Asp Gln Gln Trp Lys Thr Glu Glu Gly Leu Pro Gly Pro His 
        275                 280                 285 

Trp Gly Leu Phe Asp Ala Gln Arg Lys Ile Lys Leu Pro Leu Gln Gly 
    290                 295                 300 

Pro Val Lys Ile Arg Ala Ser Trp Arg Ser Glu Val Pro Arg Leu Val 
305                 310                 315                 320 

Ala Asp Trp Gln Pro Asp Asn Trp Arg Thr Thr Val Leu Ile Phe Ala 
                325                 330                 335 

Ala Leu Tyr Thr Leu Leu Val Gly Val Gly Ile Ser Tyr Ala Gln Pro 
            340                 345                 350 

Leu Ser Met Trp Val Ala Leu Pro Ile Ala Leu Val Trp Val Thr Ser 
        355                 360                 365 

Leu Leu Ile Gly Thr Gly Ile Gln Gly Tyr Glu Phe Leu Glu Ser Cys 
    370                 375                 380 

Trp Gly Pro Glu Lys Pro Arg Ser Phe Pro Pro Leu Arg Ala Tyr Pro 
385                 390                 395                 400 

Gly Pro Leu Pro Lys Val Ser Ile His Val Pro Cys Tyr Asn Glu Pro 
                405                 410                 415 

Pro Asp Met Val Lys Leu Thr Leu Asp Ala Leu Gln Arg Leu Asp Tyr 
            420                 425                 430 

Pro Asn Phe Glu Val Leu Ile Ile Asp Asn Asn Thr Gln Asp Pro Glu 
        435                 440                 445 

Val Trp Glu Pro Ile Glu Gln Tyr Cys Arg Gln Leu Gly Pro Arg Phe 
    450                 455                 460 

Arg Leu Phe His Val Asn Pro Leu Ser Gly Phe Lys Ser Gly Ala Leu 
465                 470                 475                 480 

Asn Tyr Leu Leu Asp Tyr Thr Ala Lys Asp Ala Glu Ile Val Ala Ala 
                485                 490                 495 

Ile Asp Ala Asp Tyr Cys Val His Arg His Trp Leu Lys His Met Ala 
            500                 505                 510 

Pro Tyr Phe Ala Cys Pro Asp Ile Ala Val Ile Gln Val Pro Gln Asp 
        515                 520                 525 

Tyr Arg Asp Gly Asp Asp Ser Leu Phe Lys Arg Cys Cys Gln Ala Glu 
    530                 535                 540 

Tyr Arg Val Phe Phe Asn Ile Gly Met Val Ile Arg Asn Asp His Asp 
545                 550                 555                 560 

Ala Ile Ile Gln His Gly Thr Met Thr Leu Ile Arg Asn Ser Val Leu 
                565                 570                 575 

Gln Arg Leu Arg Trp Ala Glu Trp Ser Ile Cys Glu Asp Ala Glu Leu 
            580                 585                 590 

Gly Leu Arg Ile Leu Glu Asn Gly Phe Ser Thr Gly Tyr Val Ala Ile 
        595                 600                 605 

Ser Tyr Gly Lys Gly Leu Ile Pro Asp Thr Phe Met Asp Phe Lys Lys 
    610                 615                 620 

Gln Arg Tyr Arg Trp Ala Tyr Gly Val Ile Gln Ile Leu Lys Arg His 
625                 630                 635                 640 

Thr Gly Ser Leu Ile Ala Gly Thr Cys Glu Ala Leu Thr Pro Ile Gln 
                645                 650                 655 

Arg Tyr His Phe Ile Ala Gly Trp Met Pro Trp Ile Ala Gly Gly Ile 
            660                 665                 670 

Asn Tyr Phe Leu Ala Ile Ala Val Leu Leu Trp Ser Met Ala Met Ile 
        675                 680                 685 

Ile Gln Pro Asp Thr Leu Glu Pro Val Pro Trp Ile Phe Ser Ser Ser 
    690                 695                 700 

Leu Leu Leu Met Phe Val Leu Gly Val Cys Lys Ala Ile Ser Leu Tyr 
705                 710                 715                 720 

Gln Arg Leu Ala Ser Thr Asp Ile Lys Asp Ala Phe Ala Ala Ile Ile 
                725                 730                 735 

Ala Ser Met Ala Leu Tyr Ser Val Val Gly Lys Ala Val Leu Ser Ser 
            740                 745                 750 

Ala Phe Thr Ser Gly Leu Pro Phe Phe Arg Thr Pro Lys Gln Thr Ser 
        755                 760                 765 

Gly Ser Gly Leu Gly Lys Ala Leu Leu Asp Val Arg Glu Asp Leu Tyr 
    770                 775                 780 

Met Ala Val Val Trp Trp Val Met Thr Val Ser Leu Cys Phe Arg Lys 
785                 790                 795                 800 

Glu Ala Ile Gly Pro Asp Leu Gly Phe Trp Val Ala Ile Met Phe Ala 
                805                 810                 815 

Gln Ser Leu Pro Tyr Val Ala Ala Met Ile Met Ala Ile Leu Ser Ala 
            820                 825                 830 

Leu Ala Asn Arg Pro Ser Arg Ser Thr Thr 
        835                 840