Abstract:
The present invention relates to DNA-based methods for universal bacterial detection, for specific detection of the common bacterial pathogens  Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Staphylococcus saprophyticus, Streptococcus pyogenes, Haemophilus influenzae  and  Moraxella catarrhalis  as well as for specific detection of commonly encountered and clinically relevant bacterial antibiotic resistance genes directly from clinical specimens or, alternatively, from a bacterial colony. The above bacterial species can account for as much as 80% of bacterial pathogens isolated in routine microbiology laboratories.  
     The core of this invention consists primarily of the DNA sequences from all species-specific genomic DNA fragments selected by hybridization from genomic libraries or, alternatively, selected from data banks as well as any oligonucleotide sequences derived from these sequences which can be used as probes or amplification primers for PCR or any other nucleic acid amplification methods. This invention also includes DNA sequences from the selected clinically relevant antibiotic resistance genes.  
     With these methods, bacteria can be detected (universal primers and/or probes) and identified (species-specific primers and/or probes) directly from the clinical specimens or from an isolated bacterial colony. Bacteria are further evaluated for their putative susceptibility to antibiotics by resistance gene detection (antibiotic resistance gene specific primers and/or probes). Diagnostic kits for the detection of the presence, for the bacterial identification of the above-mentioned bacterial species and for the detection of antibiotic resistance genes are also claimed. These kits for the rapid (one hour or less) and accurate diagnosis of bacterial infections and antibiotic resistance will gradually replace conventional methods currently used in clinical microbiology laboratories for routine diagnosis. They should provide tools to clinicians to help prescribe promptly optimal treatments when necessary. Consequently, these tests should contribute to saving human lives, rationalizing treatment, reducing the development of antibiotic resistance and avoid unnecessary hospitalizations.

Description:
BACKGROUND OF THE INVENTION  
         [0001]    Classical Identification of Bacteria  
           [0002]    Bacteria are classically identified by their ability to utilize different substrates as a source of carbon and nitrogen through the use of biochemical tests such as the API20E™ system. Susceptibility testing of Gram negative bacilli has progressed to microdilution tests. Although the API and the microdilution systems are cost-effective, at least two days are required to obtain preliminary results due to the necessity of two successive overnight incubations to isolate and identify the bacteria from the specimen. Some faster detection methods with sophisticated and expensive apparatus have been developed. For example, the fastest identification system, the autoSCAN-Walk-Away system™ identifies both Gram negative and Gram positive from isolated bacterial colonies in 2 hours and susceptibility patterns to antibiotics in only 7 hours. However, this system has an unacceptable margin of error, especially with bacterial species other than  Enterobacteriaceae  (York et al., 1992. J. Clin. Microbiol. 30:2903-2910). Nevertheless, even this fastest method requires primary isolation of the bacteria as a pure culture, a process which takes at least 18 hours if there is a pure culture or 2 to 3 days if there is a mixed culture.  
           [0003]    Urine Specimens  
           [0004]    A large proportion (40-50%) of specimens received in routine diagnostic microbiology laboratories for bacterial identification are urine specimens (Pezzlo, 1988, Clin. Microbiol. Rev. 1:268-280). Urinary tract infections (UTI) are extremely common and affect up to 20% of women and account for extensive morbidity and increased mortality among hospitalized patients (Johnson and Stamm, 1989; Ann. Intern. Med. 111:906-917). UTI are usually of bacterial etiology and require antimicrobial therapy. The Gram negative bacillus  Escherichia coli  is by far the most prevalent urinary pathogen and accounts for 50 to 60% of UTI (Pezzlo, 1988, op. cit.). The prevalence for bacterial pathogens isolated from urine specimens observed recently at the “Centre Hospitalier de 1&#39;Université Laval (CHUL)” is given in Tables 1 and 2.  
           [0005]    Conventional pathogen identification in urine specimens. The search for pathogens in urine specimens is so preponderant in the routine microbiology laboratory that a myriad of tests have been developed. The gold standard is still the classical semi-quantitative plate culture method in which a calibrated loop of urine is streaked on plates and incubated for 18-24 hours. Colonies are then counted to determine the total number of colony forming units (CFU) per liter of urine. A bacterial UTI is normally associated with a bacterial count of ≧10 7  CFU/L in urine. However, infections with less than 10 7  CFU/L in urine are possible, particularly in patients with a high incidence of diseases or those catheterized (Stark and Maki, 1984, N. Engl. J. Med. 311:560-564). Importantly, close to 80% of urine specimens tested are considered negative (&lt;10 7  CFU/L; Table 3).  
           [0006]    Accurate and rapid urine screening methods for bacterial pathogens would allow a faster identification of negative results and a more efficient clinical investigation of the patient. Several rapid identification methods (Uriscreen™, UTIscreen™, Flash Track™ DNA probes and others) were recently compared to slower standard biochemical methods which are based on culture of the bacterial pathogens. Although much faster, these rapid tests showed low sensitivities and specificities as well as a high number of false negative and false positive results (Koening et al., 1992. J. Clin. Microbiol. 30:342-345; Pezzlo et al., 1992. J. Clin. Microbiol. 30:640-684).  
           [0007]    Urine specimens found positive by culture are further characterized using standard biochemical tests to identify the bacterial pathogen and are also tested for susceptibility to antibiotics.  
           [0008]    Any Clinical Specimens  
           [0009]    As with urine specimen which was used here as an example, our probes and amplification primers are also applicable to any other clinical specimens. The DNA-based tests proposed in this invention are superior to standard methods currently used for routine diagnosis in terms of rapidity and accuracy. While a high percentage of urine specimens are negative, in many other clinical specimens more than 95% of cultures are negative (Table 4). These data further support the use of universal probes to screen out the negative clinical specimens. Clinical specimens from organisms other than humans (e.g. other primates, mammals, farm animals or live stocks) may also be used.  
           [0010]    Towards the Development of Rapid DNA-Based Diagnostic Tests  
           [0011]    A rapid diagnostic test should have a significant impact on the management of infections. For the identification of pathogens and antibiotic resistance genes in clinical samples, DNA probe and DNA amplification technologies offer several advantages over conventional methods. There is no need for subculturing, hence the organism can be detected directly in clinical samples thereby reducing the costs and time associated with isolation of pathogens. DNA-based technologies have proven to be extremely useful for specific applications in the clinical microbiology laboratory. For example, kits for the detection of fastidious organisms based on the use of hybridization probes or DNA amplification for the direct detection of pathogens in clinical specimens are commercially available (Persing et al, 1993. Diagnostic Molecular Microbiology: Principles and Applications, American Society for Microbiology, Washington, D.C.).  
           [0012]    The present invention is an advantageous alternative to the conventional culture identification methods used in hospital clinical microbiology laboratories and in private clinics for routine diagnosis. Besides being much faster, DNA-based diagnostic tests are more accurate than standard biochemical tests presently used for diagnosis because the bacterial genotype (e.g. DNA level) is more stable than the bacterial phenotype (e.g. biochemical properties). The originality of this invention is that genomic DNA fragments (size of at least 100 base pairs) specific for 12 species of commonly encountered bacterial pathogens were selected from genomic libraries or from data banks. Amplification primers or oligonucleotide probes (both less than 100 nucleotides in length) which are both derived from the sequence of species-specific DNA fragments identified by hybridization from genomic libraries or from selected data bank sequences are used as a basis to develop diagnostic tests. Oligonucleotide primers and probes for the detection of commonly encountered and clinically important bacterial resistance genes are also included. For example, Annexes I and II present a list of suitable oligonucleotide probes and PCR primers which were all derived from the species-specific DNA fragments selected from genomic libraries or from data bank sequences. It is clear to the individual skilled in the art that oligonucleotide sequences appropriate for the specific detection of the above bacterial species other than those listed in Annexes 1 and 2 may be derived from the species-specific fragments or from the selected data bank sequences. For example, the oligonucleotides may be shorter or longer than the ones we have chosen and may be selected anywhere else in the identified species-specific sequences or selected data bank sequences. Alternatively, the oligonucleotides may be designed for use in amplification methods other than PCR. Consequently, the core of this invention is the identification of species-specific genomic DNA fragments from bacterial genomic DNA libraries and the selection of genomic DNA fragments from data bank sequences which are used as a source of species-specific and ubiquitous oligonucleotides. Although the selection of oligonucleotides suitable for diagnostic purposes from the sequence of the species-specific fragments or from the selected data bank sequences requires much effort it is quite possible for the individual skilled in the art to derive from our fragments or selected data bank sequences suitable oligonucleotides which are different from the ones we have selected and tested as examples (Annexes I and II).  
           [0013]    Others have developed DNA-based tests for the detection and identification of some of the bacterial pathogens for which we have identified species-specific sequences (PCT patent application Serial No. WO 93/03186). However, their strategy was based on the amplification of the highly conserved 16S rRNA gene followed by hybridization with internal species-specific oligonucleotides. The strategy from this invention is much simpler and more rapid because it allows the direct amplification of species-specific targets using oligonucleotides derived from the species-specific bacterial genomic DNA fragments.  
           [0014]    Since a high percentage of clinical specimens are negative, oligonucleotide primers and probes were selected from the highly conserved 16S or 23S rRNA genes to detect all bacterial pathogens possibly encountered in clinical specimens in order to determine whether a clinical specimen is infected or not. This strategy allows rapid screening out of the numerous negative clinical specimens submitted for bacteriological testing.  
           [0015]    We are also developing other DNA-based tests, to be performed simultaneously with bacterial identification, to determine rapidly the putative bacterial susceptibility to antibiotics by targeting commonly encountered and clinically relevant bacterial resistance genes. Although the sequences from the selected antibiotic resistance genes are available and have been used to develop DNA-based tests for their detection (Ehrlich and Greenberg, 1994. PCR-based Diagnostics in Infectious Diseases, Blackwell Scientific Publications, Boston, Mass.; Persing et al, 1993. Diagnostic Molecular Microbiology: Principles and Applications, American Society for Microbiology, Washington, D.C.), our approch is innovative as it represents major improvements over current “gold standard” diagnostic methods based on culture of the bacteria because it allows the rapid identification of the presence of a specific bacterial pathogen and evaluation of its susceptibility to antibiotics directly from the clinical specimens within one hour.  
           [0016]    We believe that the rapid and simple diagnostic tests not based on cultivation of the bacteria that we are developing will gradually replace the slow conventional bacterial identification methods presently used in hospital clinical microbiology laboratories and in private clinics. In our opinion, these rapid DNA-based diagnostic tests for severe and common bacterial pathogens and antibiotic resistance will (i) save lives by optimizing treatment, (ii) diminish antibiotic resistance by reducing the use of broad spectrum antibiotics and (iii) decrease overall health costs by preventing or shortening hospitalizations.  
         SUMMARY OF THE INVENTION  
         [0017]    In accordance with the present invention, there is provided sequence from genomic DNA fragments (size of at least 100 base pairs and all described in the sequence listing) selected either by hybridization from genomic libraries or from data banks and which are specific for the detection of commonly encountered bacterial pathogens (i.e.  Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Staphylococcus saprophyticus, Streptococcus pyogenes, Haemophilus influenzae  and  Moraxella catarrhalis ) in clinical specimens. These bacterial species are associated with approximately 90% of urinary tract infections and with a high percentage of other severe infections including septicemia, meningitis, pneumonia, intraabdominal infections, skin infections and many other severe respiratory tract infections. Overall, the above bacterial species may account for up to 80% of bacterial pathogens isolated in routine microbiology laboratories.  
           [0018]    Synthetic oligonucleotides for hybridization (probes) or DNA amplification (primers) were derived from the above species-specific DNA fragments (ranging in sizes from 0.25 to 5.0 kilobase pairs (kbp)) or from selected data bank sequences (GenBank and EMBL). Bacterial species for which some of the oligonucleotide probes and amplification primers were derived from selected data bank sequences are  Escherichia coli, Enterococcus faecalis, Streptococcus pyogenes  and  Pseudomonas aeruginosa.  The person skilled in the art understands that the important innovation in this invention is the identification of the species-specific DNA fragments selected either from bacterial genomic libraries by hybridization or from data bank sequences. The selection of oligonucleotides from these fragments suitable for diagnostic purposes is also innovative. Specific and ubiquitous oligonucleotides different from the ones tested in the practice are considered as embodiments of the present invention.  
           [0019]    The development of hybridization (with either fragment or oligonucleotide probes) or of DNA amplification protocols for the detection of pathogens from clinical specimens renders possible a very rapid bacterial identification. This will greatly reduce the time currently required for the identification of pathogens in the clinical laboratory since these technologies can be applied for bacterial detection and identification directly from clinical specimens with minimum pretreatment of any biological specimens to release bacterial DNA. In addition to being 100% specific, probes and amplification primers allow identification of the bacterial species directly from clinical specimens or, alternatively, from an isolated colony. DNA amplification assays have the added advantages of being faster and more sensitive than hybridization assays, since they allow rapid and exponential in vitro replication of the target segment of DNA from the bacterial genome. Universal probes and amplification primers selected from the 16S or 23S rRNA genes highly conserved among bacteria, which permit the detection of any bacterial pathogens, will serve as a procedure to screen out the numerous negative clinical specimens received in diagnostic laboratories. The use of oligonucleotide probes or primers complementary to characterized bacterial genes encoding resistance to antibiotics to identify commonly encountered and clinically important resistance genes is also under the scope of this invention.  
         DETAILED DESCRIPTION OF THE INVENTION  
         [0020]    Development of Species-Specific DNA Probes  
           [0021]    DNA fragment probes were developed for the following bacterial species:  Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Haemophilus influenzae  and  Moraxella catarrhalis.  (For  Enterococcus faecalis  and Streptococcus pyogenes, oligonucleotide sequences were exclusively derived from selected data bank sequences). These species-specific fragments were selected from bacterial genomic libraries by hybridization to DNA from a variety of Gram positive and Gram negative bacterial species (Table 5).  
           [0022]    The chromosomal DNA from each bacterial species for which probes were seeked was isolated using standard methods. DNA was digested with a frequently cutting restriction enzyme such as Sau3AI and then ligated into the bacterial plasmid vector pGEM3Zf (Promega) linearized by appropriate restriction endonuclease digestion. Recombinant plasmids were then used to transform competent  E. coli  strain DH5α thereby yielding a genomic library. The plasmid content of the transformed bacterial cells was analyzed using standard methods. DNA fragments of target bacteria ranging in size from 0.25 to 5.0 kilobase pairs (kbp) were cut out from the vector by digestion of the recombinant plasmid with various restriction endonucleases. The insert was separated from the vector by agarose gel electrophoresis and purified in low melting point agarose gels. Each of the purified fragments of bacterial genomic DNA was then used as a probe for specificity tests.  
           [0023]    For each given species, the gel-purified restriction fragments of unknown coding potential were labeled with the radioactive nucleotide α- 32 P(dATP) which was incorporated into the DNA fragment by the random priming labeling reaction. Non-radioactive modified nucleotides could also be incorporated into the DNA by this method to serve as a label.  
           [0024]    Each DNA fragment probe (i.e. a segment of bacterial genomic DNA of at least 100 bp in length cut out from clones randomly selected from the genomic library) was then tested for its specificity by hybridization to DNAs from a variety of bacterial species (Table 5). The double-stranded labeled DNA probe was heat-denatured to yield labeled single-stranded DNA which could then hybridize to any single-stranded target DNA fixed onto a solid support or in solution. The target DNAs consisted of total cellular DNA from an array of bacterial species found in clinical samples (Table 5). Each target DNA was released from the bacterial cells and denatured by conventional methods and then irreversibly fixed onto a solid support (e.g. nylon or nitrocellulose membranes) or free in solution. The fixed single-stranded target DNAs were then hybridized with the single-stranded probe. Pre-hybridization, hybridization and post-hybridization conditions were as follows: (i) Pre-hybridization; in 1 M NaCl+10% dextran sulfate+1% SDS (sodium dodecyl sulfate)+1 μg/ml salmon sperm DNA at 650° C. for 15 min. (ii) Hybridization; in fresh pre-hybridization solution containing the labeled probe at 650° C. overnight. (iii) Post-hybridization; washes twice in 3×SSC containing 1% SDS (1×SSC is 0.15M NaCl, 0.015M NaCitrate) and twice in 0.1×SSC containing 0.1% SDS; all washes were at 650° C. for 15 min. Autoradiography of washed filters allowed the detection of selectively hybridized probes. Hybridization of the probe to a specific target DNA indicated a high degree of similarity between the nucleotide sequence of these two DNAs. Species-specific DNA fragments selected from various bacterial genomic libraries ranging in size from 0.25 to 5.0 kbp were isolated for 10 common bacterial pathogens (Table 6) based on hybridization to chromosomal DNAs from a variety of bacteria performed as described above. All of the bacterial species tested (66 species listed in Table 5) were likely to be pathogens associated with common infections or potential contaminants which can be isolated from clinical specimens. A DNA fragment probe was considered specific only when it hybridized solely to the pathogen from which it was isolated. DNA fragment probes found to be specific were subsequently tested for their ubiquity (i.e. ubiquitous probes recognized most isolates of the target species) by hybridization to bacterial DNAs from approximately 10 to 80 clinical isolates of the species of interest (Table 6). The DNAs were denatured, fixed onto nylon membranes and hybridized as described above.  
           [0025]    Sequencing of the Species-Specific Fragment Orobes  
           [0026]    The nucleotide sequence of the totality or of a portion of the species-specific DNA fragments isolated (Table 6) was determined using the dideoxynucleotide termination sequencing method which was performed using Sequenase (USB Biochemicals) or T7 DNA polymerase (Pharmacia). These nucleotide sequences are shown in the sequence listing. Alternatively, sequences selected from data banks (GenBank and EMBL) were used as sources of oligonucleotides for diagnostic purposes for  Escherichia coli, Enterococcus faecalis, Streptococcus pyogenes  and  Pseudomonas aeruginosa.  For this strategy, an array of suitable oligonucleotide primers or probes derived from a variety of genomic DNA fragments (size of more than 100 bp) selected from data banks was tested for their specificity and ubiquity in PCR and hybridization assays as described later. It is important to note that the data bank sequences were selected based on their potential of being species-specific according to available sequence information. Only data bank sequences from which species-specific oligonucleotides could be derived are included in this invention.  
           [0027]    Oligonucleotide probes and amplification primers derived from species-specific fragments selected from the genomic libraries or from data bank sequences were synthesized using an automated DNA synthesizer (Millipore). Prior to synthesis, all oligonucleotides (probes for hybridization and primers for DNA amplification) were evaluated for their suitability for hybridization or DNA amplification by polymerase chain reaction (PCR) by computer analysis using standard programs (e.g. Genetics Computer Group (GCG) and Oligo™ 4.0 (National Biosciences)). The potential suitability of the PCR primer pairs was also evaluated prior to the synthesis by verifying the absence of unwanted features such as long stretches of one nucleotide, a high proportion of G or C residues at the 3′ end and a 3′-terminal T residue (Persing et al, 1993. Diagnostic Molecular Microbiology: Principles and Applications, American Society for Microbiology, Washington, D.C.).  
           [0028]    Hybridization with Oligonucleotide Probes  
           [0029]    In hybridization experiments, oligonucleotides (size less than 100 nucleotides) have some advantages over DNA fragment probes for the detection of bacteria such as ease of preparation in large quantities, consistency in results from batch to batch and chemical stability. Briefly, for the hybridizations, oligonucleotides were 5′ end-labeled with the radionucleotide γ 32 P(ATP) using T4 polynucleotide kinase (Pharmacia). The unincorporated radionucleotide was removed by passing the labeled single-stranded oligonucleotide through a Sephadex G50 column. Alternatively, oligonucleotides were labeled with biotin, either enzymatically at their 3′ ends or incorporated directly during synthesis at their 5′ ends, or with digoxigenin. It will be appreciated by the person skilled in the art that labeling means other than the three above labels may be used.  
           [0030]    The target DNA was denatured, fixed onto a solid support and hybridized as previously described for the DNA fragment probes. Conditions for pre-hybridization and hybridization were as described earlier. Post-hybridization washing conditions were as follows: twice in 3×SSC containing 1% SDS, twice in 2×SSC containing 1% SDS and twice in 1×SSC containing 1% SDS (all of these washes were at 65° C. for 15 min ), and a final wash in 0.1×SSC containing 1% SDS at 25° C. for 15 min. For probes labeled with radioactive labels the detection of hybrids was by autoradiography as described earlier. For non-radioactive labels detection may be calorimetric or by chemiluminescence.  
           [0031]    The oligonucleotide probes may be derived from either strand of the duplex DNA. The probes may consist of the bases A, G, C, or T or analogs. The probes may be of any suitable length and may be selected anywhere within the species-specific genomic DNA fragments selected from the genomic libraries or from data bank sequences.  
           [0032]    DNA Amplification  
           [0033]    For DNA amplification by the widely used PCR (polymerase chain reaction) method, primer pairs were derived either from the sequenced species-specific DNA fragments or from data bank sequences or, alternatively, were shortened versions of oligonucleotide probes. Prior to synthesis, the potential primer pairs were analyzed by using the program oligo™ 4.0 (National Biosciences) to verify that they are likely candidates for PCR amplifications.  
           [0034]    During DNA amplification by PCR, two oligonucleotide primers binding respectively to each strand of the denatured double-stranded target DNA from the bacterial genome are used to amplify exponentially in vitro the target DNA by successive thermal cycles allowing denaturation of the DNA, annealing of the primers and synthesis of new targets at each cycle (Persing et al, 1993. Diagnostic Molecular Microbiology: Principles and Applications, American Society for Microbiology, Washington, D.C.). Briefly, the PCR protocols were as follows. Clinical specimens or bacterial colonies were added directly to the 50 μL PCR reaction mixtures containing 50 mM KCl, 10 mM Tris-HCl pH 8.3, 2.5 mM MgCl 2,  0.4 μM of each of the two primers, 200 μM of each of the four dNTPs and 1.25 Units of Taq DNA polymerase (Perkin Elmer). PCR reactions were then subjected to thermal cycling (3 min at 95° C. followed by 30 cycles of 1 second at 95° C. and 1 second at 55° C.) using a Perkin Elmer 480™ thermal cycler and subsequently analyzed by standard ethidium bromide-stained agarose gel electrophoresis. It is clear that other methods for the detection of specific amplification products, which may be faster and more practical for routine diagnosis, may be used. Such methods may be based on the detection of fluorescence after amplification (e.g. TaqMan™ system from Perkin Elmer or Amplisensor™ from Biotronics) or liquid hybridization with an oligonucleotide probe binding to internal sequences of the specific amplification product. These novel probes can be generated from our species-specific fragment probes. Methods based on the detection of fluorescence are particularly promising for utilization in routine diagnosis as they are, very rapid and quantitative and can be automated.  
           [0035]    To assure PCR efficiency, glycerol or dimethyl sulfoxide (DMSO) or other related solvents, can be used to increase the sensitivity of the PCR and to overcome problems associated with the amplification of target with a high GC content or with strong secondary structures. The concentration ranges for glycerol and DMSO are 5-15% (v/v) and 3-10% (v\v), respectively. For the PCR reaction mixture, the concentration ranges for the amplification primers and the MgCl 2  are 0.1-1.0 μM and 1.5-3.5 mM, respectively. Modifications of the standard PCR protocol using external and nested primers (i.e. nested PCR) or using more than one primer pair (i.e. multiplex PCR) may also be used (Persing et al, 1993. Diagnostic Molecular Microbiology: Principles and Applications, American Society for Microbiology, Washington, D.C.). For more details about the PCR protocols and amplicon detection methods see examples 7 and 8.  
           [0036]    The person skilled in the art of DNA amplification knows the existence of other rapid amplification procedures such as ligase chain reaction (LCR), transcription-based amplification systems (TAS), self-sustained sequence replication (3SR), nucleic acid sequence-based amplification (NASBA), strand displacement amplification (SDA) and branched DNA (bDNA) (Persing et al, 1993. Diagnostic Molecular Microbiology: Principles and Applications, American Society for Microbiology, Washington, D.C.). The scope of this invention is not limited to the use of amplification by PCR, but rather includes the use of any rapid nucleic acid amplification methods or any other procedures which may be used to increase rapidity and sensitivity of the tests. Any oligonucleotides suitable for the amplification of nucleic acid by approaches other than PCR and derived from the species-specific fragments and from selected antibiotic resistance gene sequences included in this document are also under the scope of this invention.  
           [0037]    Specificity and Ubiquity Tests for Oligonucleotide Probes and Primers  
           [0038]    The specificity of oligonucleotide probes, derived either from the sequenced species-specific fragments or from data bank sequences, was tested by hybridization to DNAs from the array of bacterial species listed in Table 5 as previously described. Oligonucleotides found to be specific were subsequently tested for their ubiquity by hybridization to bacterial DNAs from approximately 80 isolates of the target species as described for fragment probes. Probes were considered ubiquitous when they hybridized specifically with the DNA from at least 80% of the isolates. Results for specificity and ubiquity tests with the oligonucleotide probes are summarized in Table 6. The specificity and ubiquity of the amplification primer pairs were tested directly from cultures (see example 7) of the same bacterial strains. For specificity and ubiquity tests, PCR assays were performed directly from bacterial colonies of approximately 80 isolates of the target species. Results are summarized in Table 7. All specific and ubiquitous oligonucleotide probes and amplification primers for each of the 12 bacterial species investigated are listed in Annexes I and II, respectively. Divergence in the sequenced DNA fragments can occur and, insofar as the divergence of these sequences or a part thereof does not affect the specificity of the probes or amplification primers, variant bacterial DNA is under the scope of this invention.  
           [0039]    Universal Bacterial Detection  
           [0040]    In the routine microbiology laboratory a high percentage of clinical specimens sent for bacterial identification is negative (Table 4). For example, over a 2 year period, around 80% of urine specimens received by the laboratory at the “Centre Hospitalier de 1&#39; Université Laval (CHUL)” were negative (i.e. &lt;10 7  CFU/L) (Table 3). Testing clinical samples with universal probes or universal amplification primers to detect the presence of bacteria prior to specific identification and screen out the numerous negative specimens is thus useful as it saves costs and may rapidly orient the clinical management of the patients. Several oligonucleotides and amplification primers were therefore synthesized from highly conserved portions of bacterial 16S or 23S ribosomal RNA gene sequences available in data banks (Annexes III and IV). In hybridization tests, a pool of seven oligonucleotides (Annex I; Table 6) hybridized strongly to DNA from all bacterial species listed in Table 5. This pool of universal probes labeled with radionucleotides or with any other modified nucleotides is consequently very useful for detection of bacteria in urine samples with a sensitivity range of ≧10 7  CFU/L. These probes can also be applied for bacterial detection in other clinical samples.  
           [0041]    Amplification primers also derived from the sequence of highly conserved ribosomal RNA genes were used as an alternative strategy for universal bacterial detection directly from clinical specimens (Annex IV; Table 7). The DNA amplification strategy was developed to increase the sensitivity and the rapidity of the test. This amplification test was ubiquitous since it specifically amplified DNA from 23 different bacterial species encountered in clinical specimens.  
           [0042]    Well-conserved bacterial genes other than ribosomal RNA genes could also be good candidates for universal bacterial detection directly from clinical specimens. Such genes may be associated with processes essential for bacterial survival (e.g. protein synthesis, DNA synthesis, cell division or DNA repair) and could therefore be highly conserved during evolution. We are working on these candidate genes to develop new rapid tests for the universal detection of bacteria directly from clinical specimens.  
           [0043]    Antibiotic Resistance Genes  
           [0044]    Antimicrobial resistance complicates treatment and often leads to therapeutic failures. Furthermore, overuse of antibiotics inevitably leads to the emergence of bacterial resistance. Our goal is to provide the clinicians, within one hour, the needed information to prescribe optimal treatments. Besides the rapid identification of negative clinical specimens with DNA-based tests for universal bacterial detection and the identification of the presence of a specific pathogen in the positive specimens with DNA-based tests for specific bacterial detection, the clinicians also need timely information about the ability of the bacterial pathogen to resist antibiotic treatments. We feel that the most efficient strategy to evaluate rapidly bacterial resistance to antimicrobials is to detect directly from the clinical specimens the most common and important antibiotic resistance genes (i.e. DNA-based tests for the detection of antibiotic resitance genes). Since the sequence from the most important and common bacterial antibiotic resistance genes are available from data banks, our strategy is to use the sequence from a portion or from the entire gene to design specific oligonucleotides which will be used as a basis for the development of rapid DNA-based tests. The sequence from the bacterial antibiotic resistance genes selected on the basis of their clinical relevance (i.e. high incidence and importance) is given in the sequence listing. Table 8 summarizes some characteristics of the selected antibiotic resistance genes. 
       
    
    
     EXAMPLES  
       [0045]    The following examples are intended to be illustrative of the various methods and compounds of the invention.  
       Example 1  
       [0046]    Isolation and cloning of fragments. Genomic DNAs from  Escherichia coli  strain ATCC 25922,  Klebsiella pneumoniae  strain CK2,  Pseudomonas aeruginosa  strain ATCC 27853,  Proteus mirabilis  strain ATCC 35657,  Streptococcus pneumoniae  strain ATCC 27336,  Staphylococcus aureus  strain ATCC 25923,  Staphylococcus epidermidis  strain ATCC 12228,  Staphylococcus saprophyticus  strain ATCC 15305,  Haemophilus influenzae  reference strain Rd and  Moraxella catarrhalis  strain ATCC 53879 were prepared using standard procedures. It is understood that the bacterial genomic DNA may have been isolated from strains other than the ones mentioned above. (For  Enterococcus faecalis  and  Streptococcus pyogenes  oligonucleotide sequences were derived exclusively from data banks). Each DNA was digested with a restriction enzyme which frequently cuts DNA such as Sau3AI. The resulting DNA fragments were ligated into a plasmid vector (pGEM3Zf) to create recombinant plasmids and transformed into competent  E. coli  cells (DH5α). It is understood that the vectors and corresponding competent cells should not be limited to the ones herein above specifically examplified. The objective of obtaining recombinant plasmids and transformed cells is to provide an easily reproducible source of DNA fragments useful as probes. Therefore, insofar as the inserted fragments are specific and selective for the target bacterial DNA, any recombinant plasmids and corresponding transformed host cells are under the scope of this invention. The plasmid content of the transformed bacterial cells was analyzed using standard methods. DNA fragments from target bacteria ranging in size from 0.25 to 5.0 kbp were cut out from the vector by digestion of the recombinant plasmid with various restriction endonucleases. The insert was separated from the vector by agarose gel electrophoresis and purified in a low melting point agarose gel. Each of the purified fragments was then used for specificity tests.  
         [0047]    Labeling of DNA fragment probes. The label used was α 32 P(dATP), a radioactive nucleotide which can be incorporated enzymatically into a double-stranded DNA molecule. The fragment of interest is first denatured by heating at 95° C. for 5 min, then a mixture of random primers is allowed to anneal to the strands of the fragments. These primers, once annealed, provide a starting point for synthesis of DNA. DNA polymerase, usually the Klenow fragment, is provided along with the four nucleotides, one of which is radioactive. When the reaction is terminated, the mixture of new DNA molecules is once again denatured to provide radioactive single-stranded DNA molecules (i.e. the probe). As mentioned earlier, other modified nucleotides may be used to label the probes.  
         [0048]    Specificity and ubiquity tests for the DNA fragment probes. Species-specific DNA fragments ranging in size from 0.25 to 5.0 kbp were isolated for 10 common bacterial pathogens (Table 6) based on hybridization to chromosomal DNAs from a variety of bacteria. Samples of whole cell DNA for each bacterial strain listed in Table 5 were transferred onto a nylon membrane using a dot blot apparatus, washed and denatured before being irreversibly fixed. Hybridization conditions were as described earlier. A DNA fragment probe was considered specific only when it hybridized solely to the pathogen from which it was isolated. Labeled DNA fragments hybridizing specifically only to target bacterial species (i.e. specific) were then tested for their ubiquity by hybridization to DNAs from approximately 10 to 80 isolates of the species of interest as described earlier. The conditions for pre-hybridization, hybridization and post-hybridization washes were as described earlier. After autoradiography (or other detection means appropriate for the non-radioactive label used), the specificity of each individual probe can be determined. Each probe found to be specific (i.e. hybridizing only to the DNA from the bacterial species from which it was isolated) and ubiquitous (i.e. hybridizing to most isolates of the target species) was kept for further experimentations.  
       Example 2  
       [0049]    Same as example 1 except that testing of the strains is by colony hybridization. The bacterial strains were inoculated onto a nylon membrane placed on nutrient agar. The membranes were incubated at 37° C. for two hours and then bacterial lysis and DNA denaturation were carried out according to standard procedures. DNA hybridization was performed as described earlier.  
       Example 3  
       [0050]    Same as example 1 except that bacteria were detected directly from clinical samples. Any biological samples were loaded directly onto a dot blot apparatus and cells were lysed in situ for bacterial detection. Blood samples should be heparizined in order to avoid coagulation interfering with their convenient loading on a dot blot apparatus.  
       Example 4  
       [0051]    Nucleotide sequencina of DNA fragments. The nucleotide sequence of the totality or a portion of each fragment found to be specific and ubiquitous (Example 1) was determined using the dideoxynucleotide termination sequencing method (Sanger et al., 1977, Proc. Natl. Acad. Sci. USA. 74:5463-5467). These DNA sequences are shown in the sequence listing. Oligonucleotide probes and amplification primers were selected from these nucleotide sequences, or alternatively, from selected data banks sequences and were then synthesized on an automated Biosearch synthesizer (Millipore™) using phosphoramidite chemistry.  
         [0052]    Labeling of oliaonucleotides. Each oligonucleotide was 5′ end-labeled with γ 32 P-ATP by the T4 polynucleotide kinase (Pharmacia) as described earlier. The label could also be non-radioactive.  
         [0053]    Specificity test for oligonucleotide probes. All labeled oligonucleotide probes were tested for their specificity by hybridization to DNAs from a variety of Gram positive and Gram negative bacterial species as described earlier. Species-specific probes were those hybridizing only to DNA from the bacterial species from which it was isolated. Oligonucleotide probes found to be specific were submitted to ubiquity tests as follows.  
         [0054]    Ubiquity test for oligonucleotide probes. Specific oligonucleotide probes were then used in ubiquity tests with approximately 80 strains of the target species. Chromosomal DNAs from the isolates were transferred onto nylon membranes and hybridized with labeled oligonucleotide probes as described for specificity tests. The batteries of approximately 80 isolates constructed for each target species contain reference ATCC strains as well as a variety of clinical isolates obtained from various sources. Ubiquitous probes were those hybridizing to at least 80% of DNAs from the battery of clinical isolates of the target species. Examples of specific and ubiquitous oligonucleotide probes are listed in Annex 1.  
       Example 5  
       [0055]    Same as example 4 except that a pool of specific oligonucleotide probes is used for bacterial identification (i) to increase sensitivity and assure 100% ubiquity or (ii) to identify simultaneously more than one bacterial species. Bacterial identification could be done from isolated colonies or directly from clinical specimens.  
       Example 6  
       [0056]    PCR amplification. The technique of PCR was used to increase sensitivity and rapidity of the tests. The PCR primers used were often shorter derivatives of the extensive sets of oligonucleotides previously developed for hybridization assays (Table 6). The sets of primers were tested in PCR assays performed directly from a bacterial colony or from a bacterial suspension (see Example 7) to determine their specificity and ubiquity (Table 7). Examples of specific and ubiquitous PCR primer pairs are listed in annex II.  
         [0057]    Specificity and ubiquity tests for amplification primers. The specificity of all selected PCR primer pairs was tested against the battery of Gram negative and Gram positive bacteria used to test the oligonucleotide probes (Table 5). Primer pairs found specific for each species were then tested for their ubiquity to ensure that each set of primers could amplify at least 80% of DNAs from a battery of approximately 80 isolates of the target species. The batteries of isolates constructed for each species contain reference ATCC strains and various clinical isolates representative of the clinical diversity for each species.  
         [0058]    Standard precautions to avoid false positive PCR results should be taken. Methods to inactivate PCR amplification products such as the inactivation by uracil-N-glycosylase may be used to control PCR carryover.  
       Example 7  
       [0059]    Amplification directly from a bacterial colony or suspension. PCR assays were performed either directly from a bacterial colony or from a bacterial suspension, the latter being adjusted to a standard McFarland 0.5 (corresponds to 1.5 ×10 8  bacteria/mL). In the case of direct amplification from a colony, a portion of the colony was transferred directly to a 50 μL PCR reaction mixture (containing 50 mM KCl, 10 mM Tris pH 8.3, 2.5 mM MgCl 2,  0.4 μM of each of the two primers, 200 μM of each of the four dNTPs and 1.25 Unit of Taq DNA polymerase (Perkin Elmer)) using a plastic rod. For the bacterial suspension, 4 μL of the cell suspension was added to 46 μL of the same PCR reaction mixture. For both strategies, the reaction mixture was overlaid with 50 μL of mineral oil and PCR amplifications were carried out using an initial denaturation step of 3 min. at 95° C. followed by 30 cycles consisting of a 1 second denaturation step at 95° C. and of a 1 second annealing step at 55° C. in a Perkin Elmer 480™ thermal cycler. PCR amplification products were then analyzed by standard agarose gel (2%) electrophoresis. Amplification products were visualized in agarose gels containing 2.5 μg/mL of ethidium bromide under UV at 254 nm. The entire PCR assay can be completed in approximately one hour.  
         [0060]    Alternatively, amplification from bacterial cultures was performed as described above but using a “hot start” protocol. In that case, an initial reaction mixture containing the target DNA, primers and dNTPs was heated at 85° C. prior to the addition of the other components of the PCR reaction mixture. The final concentration of all reagents was as described above. Subsequently, the PCR reactions were submitted to thermal cycling and analysis as described above.  
       Example 8  
       [0061]    Amplification directly from clinical specimens. For amplification from urine specimens, 4 μL of undiluted or diluted (1:10) urine was added directly to 46 μL of the above PCR reaction mixture and amplified as described earlier.  
         [0062]    To improve bacterial cell lysis and eliminate the PCR inhibitory effects of clinical specimens, samples were routinely diluted in lysis buffer containing detergent(s). Subsequently, the lysate was added directly to the PCR reaction mixture. Heat treatments of the lysates, prior to DNA amplification, using the thermocycler or a microwave oven could also be performed to increase the efficiency of cell lysis.  
         [0063]    Our strategy is to develop rapid and simple protocols to eliminate PCR inhibitory effects of clinical specimens and lyse bacterial cells to perform DNA amplification directly from a variety of biological samples. PCR has the advantage of being compatible with crude DNA preparations. For example, blood, cerebrospinal fluid and sera may be used directly in PCR assays after a brief heat treatment. We intend to use such rapid and simple strategies to develop fast protocols for DNA amplification from a variety of clinical specimens.  
       Example 9  
       [0064]    Detection of antibiotic resistance genes. The presence of specific antibiotic resistance genes which are frequently encountered and clinically relevant is identified using the PCR amplification or hybridization protocols described in previous sections. Specific oligonucleotides used as a basis for the DNA-based tests are selected from the antibiotic resistance gene sequences. These tests can be performed either directly from clinical specimens or from a bacterial colony and should complement diagnostic tests for specific bacterial identification.  
       Example 10  
       [0065]    Same as examples 7 and 8 except that assays were performed by multiplex PCR (i.e. using several pairs of primers in a single PCR reaction) to (i) reach an ubiquity of 100% for the specific target pathogen or (ii) to detect simultaneously several species of bacterial pathogens.  
         [0066]    For example, the detection of Escherichia coli requires three pairs of PCR primers to assure a ubiquity of 100%. Therefore, a multiplex PCR assay (using the “hot-start” protocol (Example 7)) with those three primer pairs was developed. This strategy was also used for the other bacterial pathogens for which more than one primer pair was required to reach an ubiquity of 100%.  
         [0067]    Multiplex PCR assays could also be used to (i) detect simultaneously several bacterial species or, alternatively, (ii) to simultaneously identify the bacterial pathogen and detect specific antibiotic resistance genes either directly from a clinical specimen or from a bacterial colony.  
         [0068]    For these applications, amplicon detection methods should be adapted to differentiate the various amplicons produced. Standard agarose gel electrophoresis could be used because it discriminates the amplicons based on their sizes. Another useful strategy for this purpose would be detection using a variety of fluorochromes emitting at different wavelengths which are each coupled with a specific oligonucleotide linked to a fluorescence quencher which is degraded during amplification to release the fluorochrome (e.g. TaqMan™, Perkin Elmer).  
       Example 11  
       [0069]    Detection of amplification Products. The person skilled in the art will appreciate that alternatives other than standard agarose gel electrophoresis (Example 7) may be used for the revelation of amplification products. Such methods may be based on the detection of fluorescence after amplification (e.g. Amplisensor™, Biotronics; TaqMan™) or other labels such as biotin (SHARP Signal™ system, Digene Diagnostics). These methods are quantitative and easily automated. One of the amplification primers or an internal oligonucleotide probe specific to the amplicon(s) derived from the species-specific fragment probes is coupled with the fluorochrome or with any other label. Methods based on the detection of fluorescence are particularly suitable for diagnostic tests since they are rapid and flexible as fluorochromes emitting different wavelengths are available (Perkin Elmer).  
       Example 12  
       [0070]    Species-specific, universal and antibiotic resistance gene amplification primers can be used in other rapid amplification procedures such as the ligase chain reaction (LCR), transcription-based amplification systems (TAS), self-sustained sequence replication (3SR), nucleic acid sequence-based amplification (NASBA), strand displacement amplification (SDA) and branched DNA (bDNA) or any other methods to increase the sensitivity of the test. Amplifications can be performed from an isolated bacterial colony or directly from clinical specimens. The scope of this invention is therefore not limited to the use of PCR but rather includes the use of any procedures to specifically identify bacterial DNA and which may be used to increase rapidity and sensitivity of the tests.  
       Example 13  
       [0071]    A test kit would contain sets of probes specific for each bacterium as well as a set of universal probes. The kit is provided in the form of test components, consisting of the set of universal probes labeled with non-radioactive labels as well as labeled specific probes for the detection of each bacterium of interest in specific clinical samples. The kit will also include test reagents necessary to perform the pre-hybridization, hybridization, washing steps and hybrid detection. Finally, test components for the detection of known antibiotic resistance genes (or derivatives therefrom) will be included. Of course, the kit will include standard samples to be used as negative and positive controls for each hybridization test.  
         [0072]    Components to be included in the kits will be adapted to each specimen type and to detect pathogens commonly encountered in that type of specimen. Reagents for the universal detection of bacteria will also be included. Based on the sites of infection, the following kits for the specific detection of pathogens may be developed:  
         [0073]    A kit for the universal detection of bacterial pathogens from most clinical specimens which contains sets of probes specific for highly conserved regions of the bacterial genomes.  
         [0074]    A kit for the detection of bacterial pathogens retrieved from urine samples, which contains eight specific test components (sets of probes for the detection of  Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus saprophyticus, Staphylococcus aureus  and  Staphylococcus epidermidis ).  
         [0075]    A kit for the detection of respiratory pathogens which contains seven specific test components (sets of probes for detecting  Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Streptococcus pyogenes  and  Staphylococcus aureus ).  
         [0076]    A kit for the detection of pathogens retrieved from blood samples, which contains eleven specific test components (sets of probes for the detection of  Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, Proteus mirabilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, Streptococcus pyogenes  and  Staphylococcus epidermidis ).  
         [0077]    A kit for the detection of pathogens causing meningitis, which contains four specific test components (sets of probes for the detection of  Haemophilus influenzae, Streptococcus pneumoniae, Escherichia coli  and  Pseudomonas aeruginosa ).  
         [0078]    A kit for the detection of clinically important antibiotic resistance genes which contains sets of probes for the specific detection of at least one of the 19 following genes associated with bacterial resistance : bla tem , bla rob , bla shv , aadB, aacC1, aacC2, aacC3, aacA4, mecA, vanA, vanH, vanX, satA, aacA-aphD, vat, vga, msrA, sul and int.  
         [0079]    Other kits adapted for the detection of pathogens from skin, abdominal wound or any other clinically relevant kits will be developed.  
       Example 14  
       [0080]    Same as example 13 except that the test kits contain all reagents and controls to perform DNA amplification assays. Diagnostic kits will be adapted for amplification by PCR (or other amplification methods) performed directly either from clinical specimens or from a bacterial colony. Components required for universal bacterial detection, bacterial identification and antibiotic resistance genes detection will be included.  
         [0081]    Amplification assays could be performed either in tubes or in microtitration plates having multiple wells. For assays in plates, the wells will be coated with the specific amplification primers and control DNAs and the detection of amplification products will be automated. Reagents and amplification primers for universal bacterial detection will be included in kits for tests performed directly from clinical specimens. Components required for bacterial identification and antibiotic resistance gene detection will be included in kits for testing directly from colonies as well as in kits for testing directly from clinical specimens.  
         [0082]    The kits will be adapted for use with each type of specimen as described in example 13 for hybridization-based diagnostic kits.  
       Example 15  
       [0083]    It is understood that the use of the probes and amplification primers described in this invention for bacterial detection and identification is not limited to clinical microbiology applications. In fact, we feel that other sectors could also benefit from these new technologies. For example, these tests could be used by industries for quality control of food, water, pharmaceutical products or other products requiring microbiological control. These tests could also be applied to detect and identify bacteria in biological samples from organisms other than humans (e.g. other primates, mammals, farm animals and live stocks). These diagnostic tools could also be very useful for research purposes including clinical trials and epidemiological studies.  
                                                                     TABLE 1                           Distribution of urinary isolates from positive urine samples       (≧10 7   CFU/L) at the Centre Hospitalier       de l′Université Laval (CHUL) for the       1992-1994 period.                % of isolates                Nov 92   April 93   July 93   Jan 94       Organisms   n = 267 a     n = 265   n = 238   n = 281                      Escherichia coli     53.2   51.7   53.8   54.1         Enterococcus faecalis     13.8   12.4   11.7   11.4         Klebsiella pneumoniae     6.4   6.4   5.5   5.3         Staphylococcus epidermidis     7.1   7.9   3.0   6.4         Proteus mirabilis     2.6   3.4   3.8   2.5         Pseudomonas aeruginosa     3.7   3.0   5.0   2.9         Staphylococcus saprophyticus     3.0   1.9   5.4   1.4       Others b     10.2   13.3   11.8   16.0                                  
 
         [0084]    [0084]                                                                         TABLE 2                           Distribution of uncommon a  urinary isolates from positive urine       samples ( ≧10 7  CFU/L) at the Centre Hospitalier de       I′Université Laval (CHUL) for the 1992-1994 period.                % of isolates                Organisms a     Nov 92   April 93   July 93   Jan 94                      Staphylococcus aureus     0.4   1.1   1.3   1.4       Staphylococcus spp.   2.2   4.9   1.7   6.0       Micrococcus spp.   0.0   0.0   0.4   0.7         Enterococcus faecium     0.4   0.4   1.3   1.4       Citrobacter spp.   1.4   0.8   0.4   0.7       Enterobacter spp.   1.5   1.1   1.3   1.4         Klebsiella oxytoca     1.1   1.5   2.5   1.8       Serratia spp.   0.8   0.0   0.5   0.0       Proteus spp.   0.4   0.4   0.0   1.1       Morganella and Providencia   0.4   0.8   0.4   0.0         Hafnia alvei     0.8   0.0   0.0   0.0       NFB b  (Stenotrophomonas,   0.0   0.4   1.3   1.1       Acinetobacter)       Candida spp.   0.8   1.9   0.7   0.4                                    
         [0085]    [0085]                                               TABLE 3                           Distribution of positive a  (bacterial count ≧10 7  CFU/L)       and negative (bacterial count &lt;10 7  CFU/L) urine specimens tested       at the Centre Hospitalier de l′Université Laval (CHUL) for       the 1992-1994 period.                Number of isolates (%)            Specimens   Nov 92   April 93   July 93   Jan 94               received:   1383(100)   1338(100)   1139(100)   1345(100)       positive:    267(19.3)    265(19.8)    238(20.9)    281(20.9)       negative:   1116(80.7)   1073(80.2)    901(79.1)   1064(79.1)                            
         [0086]    [0086]                                                   TABLE 4                           Distribution of positive and negative clinical specimens tested       in the Microbiology Laboratory of the CHUL.                No. of   % of   % of       Clinical   samples   positive   negative       specimens a     tested   specimens   specimens                    Urine   17,981   19.4   80.6       Haemoculture/marrow   10,010   6.9   93.1       Sputum   1,266   68.4   31.6       Superficial pus   1,136   72.3   27.7       Cerebrospinal fluid   553   1.0   99.0       Synovial fluid-articular   523   2.7   97.3       Bronch./Trach./Amyg./Throat   502   56.6   43.4       Deep pus   473   56.8   43.2       Ears   289   47.1   52.9       Pleural and pericardial fluid   132   1.0   99.0       Peritonial fluid   101   28.6   71.4                            
         [0087]    [0087]                                 TABLE 5                           Bacterial species (66) used for testing the specificity of DNA fragment       probes, oligonucleotide probes and PCR primers.                Number of       Number of       Bacterial species   strains   Bacterial species   strains       Gram negative:   tested   Gram positive:   tested                 Proteus mirabilis     5     Streptococcus pneumoniae     7         Klebsiella pneumoniae     5     Streptococcus salivarius     2         Pseudomonas aeruginosa     5     Streptococcus viridans     2         Escherichia coli     5     Streptococcus pyogenes     2         Moraxella catarrhalis     5     Staphylococcus aureus     2         Proteus vulgaris     2     Staphylococcus epidermidis     2         Morganella morganii     2     Staphylococcus saprophyticus     5         Enterobacter cloacae     2   Micrococcus species   2         Providencia stuartii     1   Corynebacterium species   2       Providencia species   1     Streptococcus  groupe B   2         Enterobacter agglomerans     2     Staphylococcus simulans     2         Providencia rettgeri     2     Staphylococcus ludgunensis     1         Neisseria mucosa     1     Staphylococcus capitis     2         Providencia alcalifaciens     1     Staphylococcus haemolyticus     2         Providencia rustigianii     1     Staphylococcus hominis     2         Burkholderia cepacia     2     Enterococcus faecalis     2         Enterobacter aerogenes     2     Enterococcus faecium     1         Stenotrophomonas maltophilia     2     Staphylococcus warneri     1         Pseudomonas fluorescens     1     Enterococcus durans     1         Comamonas acidovorans     2     Streptococcus bovis     1         Pseudomonas putida     2   Diphteroids   2         Haemophilus influenzae     5     Lactobacillus acidophilus     1         Haemophilus parainfluenzae     2         Bordetella pertussis     2         Haemophilus parahaemolyticus     2         Haemophilus haemolyticus     2         Haemophilus aegyptius     1         Kingella indologenes     1         Moraxella atlantae     1         Neisseria caviae     1         Neisseria subflava     1         Moraxella urethralis     1         Shigella sonnei     1         Shigella flexneri     1         Klebsiella oxytoca     2         Serratia marcescens     2         Salmonella typhimurium     1         Yersinia enterocolitica     1         Acinetobacter calcoaceticus     1         Acinetobacter lwoffi     1         Haftnia alvei     2         Citrobacter diversus     1         Citrobacter freundii     1       Salmonella species   1                    
         [0088]    [0088]                                                           TABLE 6                           Species-specific DNA fragment and oligonucleotide probes for hybridization.                Number of fragment probes b     Number of oligonucleotide probes            Organisms a     Tested   Specific   Ubiquitous c     Synthesized   Specific   Ubiquitous c                   E. coli   d     —   —   —   20   12    9 f           E. coli     14   2    2 e     —   —   —         K. pneumoniae   d     —   —   —   15    1   1         K. pneumoniae     33   3   3   18   12   8         P. mirabilis   d     —   —   —    3    3   2         P. mirabilis     14   3    3 e     15    8   7         P. aeruginosa   d     —   —   —   26   13   9         P. aeruginosa      6   2    2 e      6    0   0         S. saprophyticus      7   4   4   20    9   7         H. influenzae   d     —   —   —   16    2   2         H. influenzae      1   1   1   20    1   1         S. pneumoniae   d     —   —   —    6    1   1         S. pneumoniae     19   2   2    4    1   1         M. catarrhalis      2   2   2    9    8   8         S. epidermidis     62   1   1   —   —   —         S. aureus     30   1   1   —   —   —       Universal probes d     —   —   —    7   —       7 g                                                                              
         [0089]    [0089]                                                               TABLE 7                           PCR amplification for bacterial pathogens commonly encountered in       urine, sputum, blood, cerebrospinal fluid and other specimens.                Primer pair a     Amplicon       DNA amplification            Organism   # (SEQ ID NO)   size (bp)   Ubiquity b     from colonies c     from specimens d                   E. coli     l e  (55-56)   107   75/80   +   +           2 e  (46-47)   297   77/80   +   +           3 (42-43)   102   78/80   +   +           4 (131-132)   134   73/80   +   +           1 + 3 + 4   —   80/80   +   +         E.faecalis     1 e  (38-39)   200   71/80   +   +           2 e  (40-41)   121   79/80   +   +           1 + 2   —   80/80   +   +         K. pneumoniae     1 (67-68)   198   76/80   +   +           2 (61-62)   143   67/80   +   +           3 h  (135-136)   148   78/80   +   N.T. i             4 (137-138)   116   69/80   +   N.T.           1 + 2 + 3   —   80/80   +   N.T.         P. mirabilis     1 (74-75)   167   73/80   +   N.T.           2 (133-134)   123   80/80   +   N.T.         P. aeruginosa     1 e  (83-84)   139   79/80   +   N.T.           2 e  (85-86)   223   80/80   +   N.T.         S. saprophyticus     1 (98-99)   126   79/80   +   +           2 (139-140)   190   80/80   +   N.T.         M. catarrhalis     1 (112-113)   157   79/80   +   N.T.           2 (118-119)   118   80/80   +   N.T.           3 (160-119)   137   80/80   +   N.T.         H. influenzae     1 e  (154-155)   217   80/80   +   N.T.         S. pneumoniae     1 e  (156-157)   134   80/80   +   N.T.           2 e  (158-159)   197   74/80   +   N.T.           3 (78-79)   175   67/80   +   N.T.         S. epidermidis     1 (147-148)   175   80/80   +   N.T.           2 (145-146)   125   80/80   +   N.T.         S. aureus     1 (152-153)   108   80/80   +   N.T.           2 (149-150)   151   80/80   +   N.T.           3 (149-151)   176   80/80   +   N.T.         S. pyogenes   f     1 e  (141-142)   213   80/80   +   N.T.           2 e  (143-144)   157   24/24   +   N.T.       Universal   1 e  (126-127)   241       194/195 g     +   +                            
         [0090]    a All primer pairs are specific in PCR assays since no amplification was observed with DNA from 66 different species of both Gram positive and Gram negative bacteria other than the species of interest (Table 5).  
         [0091]    b The ubiquity was normally tested on 80 strains of the species of interest. All retained primer pairs amplified at least 90% of the isolates. When combinations of primers were used, an ubiquity of 100% was reached.  
         [0092]    c For all primer pairs and multiplex combinations, PCR amplifications directly performed from a bacterial colony were 100% species-specific.  
         [0093]    d PCR assays performed directly from urine specimens.  
         [0094]    e Primer pairs derived from data bank sequences. Primer pairs with no “e” are derived from our species-specific fragments.  
         [0095]    f For S. pyogenes, primer pair #1 is specific for Group A Streptococci (GAS). Primer pair #2 is specific for the GAS-producing exotoxin A gene (SpeA).  
         [0096]    g Ubiquity tested on 195 isolates from 23 species representative of bacterial pathogens commonly encountered in clinical specimens.  
         [0097]    h Optimizations are in progress to eliminate non-specific amplification observed with some bacterial species other than the target species.  
         [0098]    N.T.: not tested.  
                                 TABLE 8                           Selected antibiotic resistance genes for diagnostic purposes.            Genes   Antibiotics   Bacteria a     SEQ ID NO               (bla tem ) TEM-1   β-lactams   Enterobacteriaceae,   161               Pseudomonadaceae,               Haemophilus, Neisseria       (bla rob ) ROB-1   β-lactams   Haemophilus, Pasteurella   162       (bla shv ) SHV-1   β-lactams   Klebsiella and other   163               Enterobacteriaceae       aadB, aacC1, aacC2,   Aminoglycosides   Enterobacteriaceae,   164, 165, 166       aacC3, aacA4       Pseudomonadaceae   167, 168       mecA   β-lactams   Staphylococci   169       vanH, vanA, vanX   Vancomycin   Enterococci   170       satA   Macrolides   Enterococci   173       aacA-aphD   Aminoglycosides   Enterococci, Staphylococci   174       vat   Macrolides   Staphylococci   175       vga   Macrolides   Staphylococci   176       msrA   Erythromycin   Staphylococci   177       Int and Sul   β-lactams, trimethoprim,   Enterobacteriaceae,   171, 172       conserved sequences   aminoglycosides, antiseptic,   Pseudomonadaceae           chloramphenicol                          
 
         [0099]    [0099]                                                                                                                                   Annex I: Specific and ubiquitous oligonucleotides probes           for hybridization                Originating DNA fragment                SEQ ID NO   Nucleotide Sequence   SEQ ID NO   Nucleotide position                    Bacterial species:  Escherichia coli                  44   5′-CAC CCG CTT GCG TGG CAA GCT GCC C    5 a     213-237                   45   5′-CGT TTG TGG ATT CCA GTT CCA TCC G    5 a     489-513               48   5′-TGA AGC ACT GGC CGA AAT GCT GCG T    6 a     759-783               49   5′-GAT GTA CAG GAT TCG TTG AAG GCT T    6 a     898-922               50   5′-TAG CGA AGG CGT AGC AGA AAC TAA C    7 a     1264-1288               51   5′-GCA ACC CGA ACT CAA CGC CGG ATT T    7 a     1227-1251               52   5′-ATA CAC AAG GGT CGC ATC TGC GGC C    7 a     1313-1337               53   5′-TGC GTA TGC ATT GCA GAC CTT GTG GC    7 a     111-136               54   5′-GCT TTC ACT GGA TAT CGC GCT TGG G    7 a     373-397                    Bacterial species:  Proteus mirabilis                  70 b     5′-TGG TTC ACT GAC TTT GCG ATG TTT C   12   23-47                   71   5′-TCG AGG ATG GCA TGC ACT AGA AAA T   12   53-77               72 b     5′-CGC TGA TTA GGT TTC GCT AAA ATC TTA TTA   12    80-109               73   5′-TTG ATC CTC ATT TTA TTA ATC ACA TGA CCA   12   174-203                                    
         [0100]    [0100]                                                                                                                                   Annex I: Specific and ubiquitous oligonucleotides probes           for hybridization                Originating DNA fragment                SEQ ID NO   Nucleotide Sequence   SEQ ID NO   Nucleotide position                    Bacterial species:  Proteus mirabilis                  76   5′-CCG CCT TTA GCA TTA ATT GGT GTT TAT AGT   13   246-275                   77   5′-CCT ATT GCA GAT ACC TTA AAT GTC TTG GGC   13   291-320               80 b     5′-TTG AGT GAT GAT TTC ACT GAC TCC C   14   18-42               81   5′-GTG AGA CAG TGA TGG TGA GGA CAC A   15 a     1185-1209               82   5′-TGG TTG TCA TGC TGT TTG TGT GAA AAT   15 a     1224-1230                    Bacterial species:  Klebsiella pneumoniae                  57   5′-GTG GTG TCG TTC AGG GGT TTC AC    8   45-67                   58   5′-GCG ATA TTC ACA CCC TAC GCA GCC A    9   161-185               59 b     5′-GTC GAA AAT GCC GGA AGA GGT ATA CG    9   203-228               60 b     5′-ACT GAG CTG CAG ACC GGT AAA ACT CA    9   233-258               63 b     5′-CGT GAT GGA TAT TCT TAA CGA AGG GC   10   250-275               64 b     5′-ACC AAA CTG TTG AGC CGC CTG GA   10   201-223               65   5′-GTG ATC GCC CCT CAT CTG CTA CT   10   77-99               66   5′-CGC CCT TCG TTA AGA ATA TCC ATC AC   10   249-274               69   5′-CAG GAA GAT GCT GCA CCG GTT GTT G   11 a     296-320                                    
         [0101]    [0101]                                                                                                                                   Annex I: Specific and ubiquitous oligonucleotides probes           for hybridization                Originating DNA fragment                SEQ ID NO   Nucleotide Sequence   SEQ ID NO   Nucleotide position                    Bacterial species:  Pseudomonas aeruginosa                   87   5′-AAT GCG GCT GTA CCT CGG CGC TGG T   18 a     2985-3009                    88   5′-GGC GGA GGG CCA GTT GCA CCT GCC A   18 a     2929-2953                89   5′-AGC CCT GCT CCT CGG CAG CCT CTG C   18 a     2821-2845                90   5′-TGG CTT TTG CAA CCG CGT TCA GGT T   18 a     1079-1103                91   5′-GCG CCC GCG AGG GCA TGC TTC GAT G   19 a     705-729                92   5′-ACC TGG GCG CCA ACT ACA AGT TCT A   19 a     668-692                93   5′-GGC TAC GCT GCC GGG CTG CAG GCC G   19 a     505-529                94   5′-CCG ATC TAG ACC ATC GAG ATG GGC G   20 a     1211-1235                95   5′-GAG CGC GGC TAT GTG TTC GTC GGC T   20 a     2111-2135                    Bacterial species:  Streptococcus pneumoniae                  120   5′-TCT GTG CTA GAG ACT GCC CCA TTT C   30   423-447                   121   5′-CGA TGT CTT GAT TGA GCA GGG TTA T   31 a     1198-1222                                    
         [0102]    [0102]                                                                                                                           Annex I: Specific and ubiquitous oligonucleotides probes           for hybridization                Originating DNA fragment                SEQ ID NO   Nucleotide Sequence   SEQ ID NO   Nucleotide position                    Bacterial species:  Staphylococcus saprophyticus                   96   5′-CGT TTT TAC CCT TAC CTT TTC GTA CTA CC   21   45-73                97 b     5′-TCA GGC AGA GGT AGT ACG AAA AGG TAA GGG   21   53-82               100   5′-CAC CAA GTT TGA CAC GTG AAG ATT CAT   22   89-115               101 b     5′-ATG AGT GAA GCG GAG TCA GAT TAT GTG CAG   23   105-134               102   5′-CGC TCA TTA CGT ACA GTG ACA ATC G   24   20-44               103   5′-CTG GTT AGC TTG ACT CTT AAC AAT CTT GTC   24   61-90               104 b     5′-GAC GCG ATT GTC ACT GTA CGT AAT GAG CGA   24   19-48                    Bacterial species:  Moraxella catarrhalis                  108   5′-GCC CCA AAA CAA TGA AAC ATA TGG T-3′   28    81-105               109   5′-CTG CAG ATT TTG GAA TCA TAT CGC C-3′   28   126-130               110   5′-TGG TTT GAC CAG TAT TTA ACG CCA T-3′   28   165-189               111   5′-CAA CGG CAC CTG ATG TAC CTT GTA C-3′   28   232-256               114   5′-TTA CAA CCT GCA CCA CAA GTC ATC A-3′   29    97-121               115   5′-GTA CAA ACA AGC CGT CAG CGA CTT A-3′   29   139-163               116   5′-CAA TCT GCG TGT GTG CGT TCA CT-3′   29   178-200               117   5′-GCT ACT TTG TCA GCT TTA GCC ATT CA-3′   29   287-312                                    
         [0103]    [0103]                                                                           Annex I:           Specific and ubiquitous oligonucleotides probes        for hybridization                     Originating DNA fragment                        SEQ ID   Nucleotide           SEQ ID NO   Nucleotide sequence   NO   position               Bacterial species:     Haemophilus influenzae                     105 b     5′-GCG TCA GAA AAA GTA GGC GAA ATG AAA G    25   138-165               106 b     5′-AGC GGC TCT ATC TTG TAA TGA CAC A   26 a     770-794               107 b     5′-GAA ACG TGA ACT CCC CTC TAT ATA A   27 a     5184-5208                   Universal probes c         122 b     5′-ATC CCA CCT TAG GCG GCT GGC TCC A   —   —               123   5′-ACG TCA AGT CAT CAT GGC CCT TAC GAG TAG G   —   —               124 b     5′-GTG TGA CGG GCG GTG TGT ACA AGG C   —   —               125 b     5′-GAG TTG CAG ACT CCA ATC CGG ACT ACG A   —   —               128 b     5′-CCC TAT ACA TCA CCT TGC GGT TTA GCA GAG AG   —   —               129   5′-GGG GGG ACC ATC CTC CAA GGC TAA ATA C   —   —               130 b     5′-CGT CCA CTT TCG TGT TTG CAG AGT GCT GTG TT   —   —                                            
         [0104]    [0104]                                                                                                                                   Annex II: Specific and ubiquitous primers for DNA amplification                    Originating DNA fragment                SEQ ID NO   Nucleotide Sequence   SEQ ID NO   Nucleotide position                    Bacterial species:  Escherichia coli                   42   5′-GCT TTC CAG CGT CAT ATT G   4   177-195                    43 b     5′-GAT CTC GAC AAA ATG GTG A   4   260-278                46   5′-TCA CCC GCT TGC GTG GC   5 a     212-228                47 b     5′-GGA ACT GGA ATC CAC AAA C   5 a     490-508                55   5′-GCA ACC CGA ACT CAA CGC C   7 a     1227-1245                56 b     5′-GCA GAT GCG ACC CTT GTG T   7 a     1315-1333               131   5′-CAG GAG TAC GGT GAT TTT TA   3   60-79               132 b     5′-ATT TCT GGT TTG GTC ATA CA   3   174-193                    Bacterial species:  Enterococcus faecalis                   38   5′-GCA ATA CAG GGA AAA ATG TC   1 a     69-88                    39 b     5′-CTT CAT CAA ACA ATT AAC TC   1 a     249-268                40   5′-GAA CAG AAG AAG CCA AAA AA   2 a     569-588                41 b     5′-GCA ATC CCA AAT AAT ACG GT   2 a     670-689                                    
         [0105]    [0105]                                                                                                                                   Annex II: Specific and ubiquitous primers for DNA amplification                    Originating DNA fragment                SEQ ID NO   Nucleotide Sequence   SEQ ID NO   Nucleotide position                    Bacterial species:  Klebsiella pneumoniae                   61   5′-GAC AGT CAG TTC GTC AGC C    9   37-55                    62 b     5′-CGT AGG GTG TGA ATA TCG C    9   161-179                67   5′-TCG CCC CTC ATC TGC TAC T   10   81-99                68 b     5′-GAT CGT GAT GGA TAT TCT T   10   260-278               135   5′-GCA GCG TGG TGT CGT TCA    8   40-57               136 b     5′-AGC TGG CAA CGG CTG GTC    8   170-187               137   5′-ATT CAC ACC CTA CGC AGC CA    9   166-185               138 b     5′-ATC CGG CAG CAT CTC TTT GT    9   262-281                    Bacterial species:  Proteus mirabilis               74   5′-GAA ACA TCG CAA AGT CAG T   12   23-41                    75 b     5′-ATA AAA TGA GGA TCA AGT TC   12   170-189               133   5′-CGG GAG TCA GTG AAA TCA TC   14   17-36               134 b     5′-CTA AAA TCG CCA CAC CTC TT   14   120-139                                    
         [0106]    [0106]                                                                                                                                                                       Annex II: Specific and ubiquitous primers for DNA amplification                    Originating DNA fragment                SEQ ID NO   Nucleotide Sequence   SEQ ID NO   Nucleotide position                    Bacterial species:  Staphylococcus saprophyticus                   98   5′-CGT TTT TAC CCT TAC CTT TTC GTA CT   21   45-70                    99 b     5′-ATC GAT CAT CAC ATT CCA TTT GTT TTT A   21   143-170               139   5′-CTG GTT AGC TTG ACT CTT AAC AAT C   24   61-85               140 b     5′-TCT TAA CGA TAG AAT GGA GCA ACT G   24   226-250                    Bacterial species:  Pseudomonas aeruginosa                   83   5′-CGA GCG GGT GGT GTT CAT C   16 a     554-572                    84 b     5′-CAA GTC GTG GTG GGA GGG A   16 a     674-692                85   5′-TCG CTG TTC ATC AAG ACC C   17 a     1423-1441                86 b     5′-CCG AGA ACC AGA CTT CAT C   17 a     1627-1645                    Bacterial species:  Moraxella catarrhalis                  112   5′-GGC ACC TGA TGT ACC TTG   28   235-252                   113 b     5′-AAC AGC TCA CAC GCA TT   28   375-391               118   5′-TGT TTT GAG CTT TTT ATT TTT TGA   29   41-64               119 b     5′-CGC TGA CGG CTT GTT TGT ACC A   29   137-158               160   5′-GCT CAA ATC AGG GTC AGC   29   22-39               119 b     5′-CGC TGA CGG CTT GTT TGT ACG A   29   137-158                                    
         [0107]    [0107]                                                                                                                                       Annex II: Specific and ubiquitous primers for DNA amplification                    Originating DNA fragment                SEQ ID NO   Nucleotide Sequence   SEQ ID NO   Nucleotide position                    Bacterial species: Staphylococcus epidermidis                145   5′-ATC AAA AAG TTG GCG AAC CTT TTC A   36   21-45                   146 b     5′-CAA AAG AGC GTG GAG AAA AGT ATC A   36   121-145               147   5′-TCT CTT TTA ATT TCA TCT TCA ATT CCA TAG   36   448-477               148 b     5′-AAA CAC AAT TAC AGT CTG GTT ATC CAT ATC   36   593-622                    Bacterial species: Staphylococcus aureus                149 b     5′-CTT CAT TTT ACG GTG ACT TCT TAG AAG ATT   37   409-438                   150   5′-TCA ACT GTA GCT TCT TTA TCC ATA CGT TGA   37   288-317               149 b     5′-CTT CAT TTT ACG GTG ACT TCT TAG AAG ATT   37   409-438               151   5′-ATA TTT TAG CTT TTC AGT TTC TAT ATC AAC   37   263-292               152   5′-AAT CTT TGT CGG TAC ACG ATA TTC TTC ACG   37    5-34               153 b     5′-CGT AAT GAG ATT TCA GTA GAT AAT ACA ACA   37   83-112                                    
         [0108]    [0108]                                                                                                                                                                   Annex II: Specific and ubiquitous primers for DNA amplification                    Originating DNA fragment                SEQ ID NO   Nucleotide Sequence   SEQ ID NO   Nucleotide position                    Bacterial species:  Haemophilus influenzae              154   5′-TTT AAC GAT CCT TTT ACT CCT TTT G   27 a     5074-5098                   155 b     5′-ACT GCT GTT GTA AAG AGG TTA AAA T   27 a     5266-5290                    Bacterial species:  Streptococcus pneumoniae                   78   5′-AGT AAA ATG AAA TAA GAA CAG GAC AG   34   164-189                    79 b     5′-AAA ACA GGA TAG GAG AAC GGG AAA A   34   314-338               156   5′-ATT TGG TGA CGG GTG ACT TT   31 a     1401-1420               157 b     5′-GCT GAG GAT TTG TTC TTC TT   31 a     1515-1534               158   5′-GAG CGG TTT CTA TGA TTG TA   35 a     1342-1361               159 b     5′-ATC TTT CCT TTC TTG TTC TT   35 a     1519-1538                    Bacterial species:  Streptococcus pyogenes                  141   5′-TGA AAA TTC TTG TAA CAG GC   32 a     286-305                   142 b     5′-GGC CAC CAG CTT GCC CAA TA   32 a     479-498               143   5′-ATA TTT TCT TTA TGA GGG TG   33 a     966-985               144 b     5′-ATC CTT AAA TAA AGT TGC CA   33 a     1103-1122                                    
         [0109]    [0109]                                                                                               Annex II: Specific and ubiquitous primers for DNA amplification                    Originating DNA fragment                SEQ ID NO   Nucleotide Sequence   SEQ ID NO   Nucleotide position                    Universal primers c              126   5′-GGA GGA AGG TGG GGA TGA CG   —   —                   127 b     5′-ATG GTG TGA CGG GCG GTG TG   —   —                                            
         [0110]    [0110]                                                               Annex III           Selection of Universal Probes by Alignment of the       Sequences of Bacterial 16S and 23S Ribosomal RNA Genes.            Reverse strand of SEQ ID NO: 122     TGGAGCC AGCCGCCTA GGTGGGAT                          1461      1510             Streptococcus salivarius     TGAGGTAACC TTT TGGAGCC AGCCGCCTAA GGTGGGAT AG ATGANNGGGG                 Proteus vulgaris     TAGCTTAACC TTC GGGAGGG CGCTTACCAC TTTGTGAT TC ATGACTGGGG                 Pseudomonas aeruginosa     TAGTCTAACC GCA AGGGGGA CGGTTACCAC GGAGTGAT TC ATGACTGGGG                 Neisseria gonorrhoeae     TAGGGTAACC GCA AGGAGTC CGCTTACCAC GGTATGCT TC ATGACTGGGG                 Streptococcus lactis     TTGCCTAACC GCA AGGAGGG CGCTTCCTAA GGTAAGAC CG ATGACNNGGG                    
         [0111]    [0111]                                                 Annex III. Selection of universal probes by alignment of the           sequences of bacterial 165 and 23S ribosomal RNA genes.                                SEQ ID NO: 123              ACGTCAAGTC ATCATGGC CCTTACGAGT AGG                       1251                                              1300         Haemophilus influenzae     GGTNGGGATG ACGTCAAGTC ..ATCATGGC CCTTACGAGT AGGGCTACAC                 Neisseria gonorrhoeae     GGTGGGGATG ACGTCAAGTC ..CTCATGGC CCTTATGACC AGGGCTTCAC                 Pseudomonas cepacia     GGTNGGGATG ACGTCAAGTC ..CTCATGGC CCTTATGGGT AGGGCTTCAC                 Serratia marcescens     GGTGGGGATG ACGTCAAGTC ..ATCATGGC CCTTACGAGT AGGGCTACAC                 Escherichia coli     GGTGGGGATG ACGTCAAGTC ..ATCATGGC CCTTACGACC AGGGCTACAC                 Proteus vulgaris     GGTGGGGATG ACGTTAAGTC GTATCATGGC CCTTACGAGT AGGGCTACAC                 Pseudomonas aeruginosa     GGTGGGGATG ACGTCAAGTC ..ATCATGGC CCTTACGGCN AGGGCTACAC                 Clostridium perfringens     GGTGGGGATG ACGTNNAATC ..ATCATGCC CNTTATGTGT AGGGCTACAC                 Mycoplasma hominis     GGTGGGGATG ACGTCAAATC ..ATCATGCC TCTTACGAGT GGGGCCACAC                 Helicobacter pylori     GGTGGGGACG ACGTCAAGTC ..ATCATGGC CCTTACGCCT AGGGCTACAC                 Mycoplasma pneumoniae     GGAAGGGATG ACGTCAAATC ..ATCATGCC CCTTATGTCT AGGGCTGCAA                    
         [0112]    [0112]                                                 Annex III. Selection of universal probes by alignment of the           sequences of bacterial 16S and 23S ribosomal RNA genes.                                Reverse of the probe SEQ ID NO: 124              GCCTTGTACA CACCGCCCGT CACAC                       1451                                   1490         Escherichia coli     ACGTTCCCGG GCCTTGTACA CACCGCCCGT CACACCATGG                 Neisseria gonorrhoeae     ACGTTCCCNG NNCTTGTACA CACCGCCCGT CACACCATGG                 Pseudomonas cepacia     ACGTTCCCGG GTCTTGTACA CACNGCCCGT CACACCATGG                 Serratia marcescens     ACGTTCCCGG GCCTTGTACA CACCGCCCGT CACACCATGG                 Proteus vulgaris     ACGTTCCCGG GCCTTGTACA CACCGCCCGT CACACCATGG                 Haemophilus influenzae     ACGTTCCCGG GCNTTGTACA CACCGCCCGT CACACCATGG                 Pseudomonas aeruginosa     ACGTTCCCGG GCCTTGTACA CACCGCCCGT CACACCATGG                 Clostridium perfringens     ACGTTCCCNG GTCTTGTACA CACCGCNCGT CACACCATGA                 Mycoplasma hominis     ACGTTCTCGG GTCTTGTACA CACCGCCCGT CACACCATGG                 Helicobacter pylori     ACGTTCCCGG GTCTTGTACT CACCGCCCGT CACACCATGG                 Mycoplasma pneumoniae     ACGTTCTCGG GTCTTGTACA CACCGCCCGT CAAACTATGA                    
         [0113]    [0113]                                                 Annex III. Selection of universal probes by alignment of the           sequences of bacterial 16S and 23S ribosomal RNA genes.                                Reverse strand of SEQ ID NO 125:          TCG TAGTCCGGAT TGGAGTCTGC AACTC                       1361                                   1400         Escherichia coli     AAGTGCGTCG TAGTCCGGAT TGGAGTCTGC AACTCGACTC                 Neisseria gonorrhoeae     AAACCGATCG TAGTCCGGAT TGCACTCTGC AACTCGAGTG                 Pseudomonas cepacia     AAACCGATCG TAGTCCGGAT TGCACTCTGC AACTCGAGTG                 Serratia marcescens     AAGTATGTCG TAGTCCGGAT TGGAGTCTGC AACTCGACTC                 Proteus vulgaris     AAGTCTGTCG TAGTCCGGAT TGGAGTCTGC AACTCGACTC                 Haemophilus influenzae     AAGTACGTCT AAGTCCGGAT TGGAGTCTGC AACTCGACTC                 Pseudomonas aeruginosa     AAACCGATCG TAGTCCGGAT CGCAGTCTGC AACTCGACTG                 Clostridium perfringens     AAACCAGTCT CAGTTCGGAT TGTAGGCTGA AACTCGCCTA                 Mycoplasma hominis     AAGCCGATCT CAGTTCGGAT TGGAGTCTGC AATTCGACTC                 Helicobacter pylori     ACACC..TCT CAGTTCGGAT TGTAGGCTGC AACTCGCCTG                 Mycloplasma pneumoniae     AAGTTGGTCT CAGTTCGGAT TGAGGGCTGC AATTCGTCCT                    
         [0114]    [0114]                                                 Annex III. Selection of universal probes by alignment of the           sequences of bacterial 16S and 23S ribosomal RNA genes.                                Reverse strand of SEQ ID NO: 128           CT CTCTGCTAAA CCGCAAGGTG ATGTATAGGG                       1991                                              2040         Lactobacillus lactis     AAACACAGCT CTCTGCTAAA CCGCAAGGTG ATGTATAGGG GGTGACGCCT                 Escherichia coli     AAACACAGCA CTGTGCAAAC ACGAAAGTGG ACGTATACGG TGTGACGCCT                 Pseudomonas aeruginosa     AAACACAGCA CTCTGCAAAC ACGAAAGTGG ACGTATAGGG TGTGACGCCT                 Pseudomonas cepacia     AAACACAGCA CTCTGCAAAC ACGAAAGTGG ACGTATAGGG TGTGACGCCT                 Bacillus stearothermophilus     AAACACAGGT CTCTGCGAAG TCGTAAGGCG ACGTATAGGG GCTGACACCT                 Micrococcus luteus     AAACACAGGT CCATGCGAAG TCGTAAGACG ATGTATATGG ACTGACTCCT               SEQ ID NO: 129              GGGGGGACC ATCCTCCAAG GCTAAATAC                   481                                                530         Escherichia coli     TGTCTGAATA TGGGGGGACC ATCCTCCAAG GCTAAATACT CCTGACTGAC                 Pseudomonas aeruginosa     TGTCTGAACA TGGGGGGACC ATCCTCCAAG GCTAAATACT ACTGACTGAC                 Pseudomonas cepacia     TGTCTGAAGA TGGGGGGACC ATCCTCCAAG GCTAAATACT CGTGATCGAC                 Lactobacillus lactis     AGTTTGAATC CGGGAGGACC ATCTCCCAAC CCTAAATACT CCTTAGTGAC                 Micrococcus luteus     CGTGTGAATC TGCCAGGACC ACCTGGTAAG CCTGAATACT ACCTGTTGAC                    
         [0115]    [0115]                                                 Annex III. Selection of universal probes by alignment of the           sequences of bacterial 16S and 23S ribosomal RNA genes.                                Reverse strand of SEQ ID NO: 130               AACACAGCA CTCTGCAAAC ACGAAAGTGG ACG                       1981                                              2030         Pseudomonas aeruginosa     TGTTTATTAA AAACACAGCA CTCTGCAAAC ACGAAAGTGG ACGTATAGGG                 Escherichia coli     TGTTTATTAA AAACACAGCA CTGTGCAAAC ACGAAAGTGG ACGTATACGG                 Pseudomonas cepacia     TGTTTAATAA AAACACAGCA CTCTGCAAAC ACGAAAGTGG ACGTATAGGG                 Bacillus stearothermophilus     TGTTTATCAA AAACACAGGT CTCTGCGAAG TCGTAAGGCG ACGTATAGGG                 Lactobacillus lactis     TGTTTATCAA AAACACAGCT CTCTGCTAAA CCACAAGGTG ATGTATAGGG                 Micrococcus luteus     TGTTTATCAA AAACACAGGT CCATGCGAAG TCGTAAGACG ATGTATATGG                    
         [0116]    [0116]                                                 Annex IV. Selection of the universal PCR primers by alignment of the bacterial           16S ribosomal RNA gene                                SEQ ID NO: 126      GGAGGAA GGTGGGGATG ACG                   Reverse strand of SEQ ID NO: 127                                                 CA CACCGCCCGT CACACCAT                   1241                        1270......1461                        1490         Escherichia coli     ACTGGAGGAA GGTGGGGATG ACGTCAAGTC......GCCTTGTACA CACCGCCCGT CACACCATGG                 Neisseria gonorrhoeae     GCCGGAGGAA GGTGGGGATG ACGTCAAGTC......NNCTTGTACA CACCGCCCGT CACACCATGG                 Pseudomonas cepacia     ACCGGAGGAA GGTNGGGATG ACGTCAAGTC......GTCTTGTACA CACNGCCCGT CACACCATGG                 Seratia marcescens     ACTGGAGGAA GGTGGGGATG ACGTCAAGTC......GCCTTGTACA CACCGCCCGT CACACCATGG                 Proteus vulgaris     ACCGGAGGAA GGTGGGGATG ACGTTAAGTC......GCCTTGTACA CACCGCCCGT CACACCATGG                 Haemophilus influenzae     ACTGGAGGAA GGTNGGGATG ACGTCAAGTC......GCNTTGTACA CACCGCCCGT CACACCATGG                 Legionella pneumophila     ACCGGAGGAA GGCGGGGATG ACGTCAAGTC......GCCTTGTACA CACCGCCCGT CACACCATGG                 Pseudomonas aeruginos     ACCGGAGGAA GGTGGGGATG ACGTCAAGTC......GCCTTGTACA CACCGCCCGT CACACCATGG                 Clostridium perfringens     CCAGGAGGAA GGTGGGGATG ACGTNNAATC......GTCTTGTACA CACCGCNCGT CACACCATGA                 Mycoplasma hominis     CTGGGAGGAA GGTGGGGATG ACGTCAAATC......GTCTTGTACA CACCGCCCGT CACACCATGG                 Helicobacter pylori     GGAGGAGGAA GGTGGGGACG ACGTCAAGTC......GTCTTGTACT CACCGCCCGT CACACCATGG                 Mycoplasma pneumoniae     ATTGGAGGAA GGAAGGGATG ACGTCAAATC......GTCTTGTACA CACCGCCCGT CAAACTATGA                    
         [0117]    [0117] 
     
       
       
         1 
         
           
             177  
           
           
             1  
             1817  
             DNA  
             Enterococcus faecalis  
           
            1 

acagtaaaaa agttgttaac gaatgaattt gttaacaact tttttgctat ggtattgagt     60 

tatgaggggc aatacaggga aaaatgtcgg ctgattaagg aatttagata gtgccggtta    120 

gtagttgtct ataatgaaaa tagcaacaaa tatttacgca gggaaagggg cggtcgttta    180 

acgggaaaaa ttagggagga taaagcaata cttttgttgg gaaaagaaat aaaaggaaac    240 

tggggaagga gttaattgtt tgatgaaggg aaataaaatt ttatacattt taggtacagg    300 

catctttgtt ggaagttcat gtctattttc ttcacttttt gtagccgcag aagaacaagt    360 

ttattcagaa agtgaagttt caacagtttt atcgaagttg gaaaaggagg caatttctga    420 

ggcagctgct gaacaatata cggttgtaga tcgaaaagaa gacgcgtggg ggatgaagca    480 

tcttaagtta gaaaagcaaa cggaaggcgt tactgttgat tcagataatg tgattattca    540 

tttagataaa aacggtgcag taacaagtgt tacaggaaat ccagttgatc aagttgtgaa    600 

aattcaatcg gttgatgcaa tcggtgaaga aggagttaaa aaaattgttg cttctgataa    660 

tccagaaact aaagatcttg tctttttagc tattgacaaa cgtgtaaata atgaagggca    720 

attattttat aaagtcagag taacttcttc accaactggt gaccccgtat cattggttta    780 

taaagtgaac gctacagatg gaacaattat ggaaaaacaa gatttaacgg aacatgtcgg    840 

tagtgaagta acgttaaaaa actcttttca agtaacgttt aatgtaccag ttgaaaaaag    900 

caatacggga attgctttac acggaacgga taacacaggg gtttaccatg cagtagttga    960 

tggcaaaaat aattattcta ttattcaagc gccatcacta gcgacattaa atcagaatgc   1020 

tattgacgcc tatacgcatg gaaaatttgt gaaaacatat tatgaagatc atttccaacg   1080 

acacagtatt gatgatcgag ggatgcccat cttgtcagtt gttgatgaac aacatccaga   1140 

tgcttatgac aatgcttttt gggatggaaa agcaatgcgt tatggtgaaa caagtacacc   1200 

aacaggaaaa acgtatgctt cctctttaga tgtagttggt catgaaatga cacatggtgt   1260 

gacggaacat actgccggtt tagaatattt aggacaatca ggtgccttga atgaatctta   1320 

ttctgatttg atgggttata ttatttcggg tgcatctaat ccagaaattg gtgcggatac   1380 

tcagagtgtt gaccgaaaaa caggtattcg aaatttacaa acgccaagta aacacggaca   1440 

accagaaacc atggctcaat acgacgatcg agcacggtat aaaggaacgc cttattatga   1500 

tcaaggcggt gttcattata acagtggaat tattaatcgg attggttaca ccattatcca   1560 

gaacttaggc attgaaaaag cacagactat tttctacagc tcgttagtaa attacttaac   1620 

acctaaagca caattcagtg atgctcgtga tgcgatgctt gctgctgcaa aagttcaata   1680 

tggcgatgaa gcagcttcag tggtgtcagc agcctttaac tctgctggaa tcggagctaa   1740 

agaagacatt caggtaaacc aaccaagtga atctgttctg gtcaatgaat gaaaaaaatt   1800 

ccccaattaa ataaaaa                                                  1817 

 
           
             2  
             2275  
             DNA  
             Enterococcus faecalis  
           
            2 

ggtaccaaag aaaaaaacga acgccacaac caacagcctc taaagcaaca cctgcttctg     60 

aaattgaggg agatttagca aatgtcaatg agattctttt ggttcacgat gatcgtgtcg    120 

ggtcagcaac gatgggaatg aaagtcttag aagaaatttt agataaagag aaaatttcaa    180 

tgccgattcg aaaaattaat attaatgaat taactcaaca aacacaggct ttaattgtca    240 

caaaagctga actaacggaa caagcacgta aaaaagcacc gaaagcgaca cacttatcag    300 

taaaaagtta tggttaatcc ccaaaaatat gaaacagtgg gtttcgctct taaaagaaag    360 

tgcctagaga ggaagaaaac aatggaaaat cttacgaata tttcaattga attaaatcaa    420 

cagtttaata caaaagaaga agctattcgc ttttccggcc agaaactagt cgaggcaggc    480 

tgtgttgagc ccgcttatat cgaagcaatg attgaaagag accaattgct atctgcccat    540 

atggggaatt ttattgccat tcctcatgga acagaagaag ccaaaaaatt agtgaaaaaa    600 

tcaggaatct gtgtagtgca agtcccagag ggcgttaatt ttggcaccga agaagatgaa    660 

aaaattgcta ccgtattatt tgggattgcc ggagtcggtg aagaacattt gcaattagtc    720 

caacaaattg cactttattg tagtgatatg gataacgtgg tgcaacttgc cgatgcatta    780 

agtaaagaag aaataacaga aaatttagcc attgcttaaa ggagagaata agaatgaacg    840 

cagtacattt tggagcagga aatattggac gcggctttat tggcgaaatt ttagctaaaa    900 

cgggtttcat attaccgttt gtggatgtta atggaaacca tcatcaagcg ttaaaagaac    960 

gtaaaagtta tacaattgaa ttggccgatg cctcacatca acaaattaac gttgaaaatg   1020 

tgaccgggtt aaataacatg acagaaccag aaaaagtagt agaagcaatt gcggaagccg   1080 

atttagtcac gacggcaatt ggtcctaata ttttaccaag aattgctgaa ttaattgctc   1140 

aaggaattga tgcacgtgcc gaagcaaatt gtcaaaacgg cccgctggat attatcgctt   1200 

gtgaaaatat gattggtggt tcaacctttt tagcagaaga agtggccata atatttgaaa   1260 

aacccagctt atctgaacaa tggattggtt ttcctgatgc ggcagttgat cggattgttc   1320 

cattacaaaa acataaagat ccactttttg ttcaagttga gcctttttgt gaatgggtca   1380 

ttgatgatac caaccgaaaa gccaaagaga ttcagttaga aggcgtcatt acttgtcgat   1440 

tagagccgta tattgaacga aaattattta gtgtaaccag tggccatgct acagttgcct   1500 

atacaggggc gttgttaggc tatcaaacca ttgacgaagc gatgcaggac gccttagtgg   1560 

tagcgcaact caaatcagtt ttgcaggaaa ccggtaaact tttagtggcc aaatggaatt   1620 

ttgatgaaca agaacatgca gcctatattg aaaaaattat caaccgtttc caaaataaat   1680 

atatttcaga tgctattaca cgtgtagcac ggacaccaat cagaaaatta ggtgcgcaag   1740 

aacggtttat tcgaccaatc cgtgaattac aggaacgcaa tctagtgtcg gccgcattta   1800 

tagcaatgat tggtattgtc tttaattatc atgatccaga agatgaacaa agccgtcaat   1860 

tacaggaaat gcttgaccaa gaaagtgttg atacagtgga tcgctgaagt aacgggcatt   1920 

gaagatccag aaacggttaa aaatattaaa caaaacgtag aactgctatg cgcgaccaca   1980 

agtagcataa ttaacaaaat ccttctacca agatacttca catttcttaa ttaaagaaaa   2040 

aacaaccgcg cctcacctga gccgaccccc aaaagttaga cctagaaatc taacttttgg   2100 

aggttttttt gtatggcaaa atacagtttt gaaatttaaa cttaaacttg ttcatgacta   2160 

cttatatggt caaggaggtc taaggtttct cgcaaagaag tatgggttta aagatagtct   2220 

caaataagca aatggataaa tgcctataaa gaacttggtg aagaaggggg gatcc        2275 

 
           
             3  
             227  
             DNA  
             Escherichia coli  
           
            3 

gatccgccat gggttgtttt ccgattgagg attttataga tggtttctgg cgacctgcac     60 

aggagtacgg tgatttttaa ttattgcaat tgcacaagag tcagttctcc cccaaagaca    120 

gcaccggtat caatataatg caggttgcca atatccacgc gatggcgcaa aggtgtatga    180 

ccaaaccaga aatgatcggc cacctgcatc gccagttcgc gagtcgg                  227 

 
           
             4  
             278  
             DNA  
             Escherichia coli  
           
            4 

gatctaaatc aaattaattg gttaaagata accacagcgg ggccgacata aactctgaca     60 

agaagttaac aaccatataa cctgcacagg acgcgaacat gtcttctcat ccgtatgtca    120 

cccagcaaaa taccccgctg gcggacgaca ccactctgat gtccactacc gatctcgctt    180 

tccagcgtca tattggggcg cgctacgttg gggcgtgggc gtaattggtc aatcaggcgc    240 

ggggtcagcg gataaacatt caccattttg tcgagatc                            278 

 
           
             5  
             1596  
             DNA  
             Escherichia coli  
           
            5 

atggctgaca ttctgctgct cgataatatc gactctttta cgtacaacct ggcagatcag     60 

ttgcgcagca atgggcataa cgtggtgatt taccgcaacc atataccggc gcaaacctta    120 

attgaacgct tggcgaccat gagtaatccg gtgctgatgc tttctcctgg ccccggtgtg    180 

ccgagcgaag ccggttgtat gccggaactc ctcacccgct tgcgtggcaa gctgcccatt    240 

attggcattt gcctcggaca tcaggcgatt gtcgaagctt acgggggcta tgtcggtcag    300 

gcgggcgaaa ttctccacgg taaagcctcc agcattgaac atgacggtca ggcgatgttt    360 

gccggattaa caaacccgct gccggtggcg cgttatcact cgctggttgg cagtaacatt    420 

ccggccggtt taaccatcaa cgcccatttt aatggcatgg tgatggcagt acgtcacgat    480 

gcggatcgcg tttgtggatt ccagttccat ccggaatcca ttctcaccac ccagggcgct    540 

cgcctgctgg aacaaacgct ggcctgggcg cagcataaac tagagccagc caacacgctg    600 

caaccgattc tggaaaaact gtatcaggcg cagacgctta gccaacaaga aagccaccag    660 

ctgttttcag cggtggtgcg tggcgagctg aagccggaac aactggcggc ggcgctggtg    720 

agcatgaaaa ttcgcggtga gcacccgaac gagatcgccg gggcagcaac cgcgctactg    780 

gaaaacgcag cgccgttccc gcgcccggat tatctgtttg ctgatatcgt cggtactggc    840 

ggtgacggca gcaacagtat caatatttct accgccagtg cgtttgtcgc cgcggcctgt    900 

gggctgaaag tggcgaaaca cggcaaccgt agcgtctcca gtaaatctgg ttcgtccgat    960 

ctgctggcgg cgttcggtat taatcttgat atgaacgccg ataaatcgcg ccaggcgctg   1020 

gatgagttag gtgtatgttt cctctttgcg ccgaagtatc acaccggatt ccgccacgcg   1080 

atgccggttc gccagcaact gaaaacccgc accctgttca atgtgctggg gccattgatt   1140 

aacccggcgc atccgccgct ggcgttaatt ggtgtttata gtccggaact ggtgctgccg   1200 

attgccgaaa ccttgcgcgt gctggggtat caacgcgcgg cggtggtgca cagcggcggg   1260 

atggatgaag tttcattaca cgcgccgaca atcgttgccg aactgcatga cggcgaaatt   1320 

aaaagctatc agctcaccgc agaagacttt ggcctgacac cctaccacca ggagcaactg   1380 

gcaggcggaa caccggaaga aaaccgtgac attttaacac gtttgttaca aggtaaaggc   1440 

gacgccgccc atgaagcagc cgtcgctgcg aacgtcgcca tgttaatgcg cctgcatggc   1500 

catgaagatc tgcaagccaa tgcgcaaacc gttcttgagg tactgcgcag tggttccgct   1560 

tacgacagag tcaccgcact ggcggcacga gggtaa                             1596 

 
           
             6  
             2703  
             DNA  
             Escherichia coli  
           
            6 

gacgacttag ttttgacgga atcagcatag ttaatcactt cactgtggaa aatgaggaaa     60 

tattattttt tttgcgcttc gtaattaatg gttataaggt cggccagaaa cctttctaat    120 

gcaagcgatg acgttttttt atgtgtctga atttgcactg tgtcacaatt ccaaatcttt    180 

attaacaact cacctaaaac gacgctgatc cagcgtgaat actggtttcc cttatgttca    240 

tcagattcat ttaagcaagg gtttcttctt cattcctgat gaaagtgcca tctaaaaaga    300 

tgatcttaat aaatctatta agaatgagat ggagcacact ggatatttta cttatgaaac    360 

tgtttcactc ctttacttaa tttatagagt taccttccgc tttttgaaaa tacgcaacgg    420 

ccattttttg cacttagata cagattttct gcgctgtatt gcattgattt gatgctaatc    480 

ctgtggtttg cactagcttt aagtggttga gatcacattt ccttgctcat ccccgcaact    540 

cctccctgcc taatcccccg caggatgagg aaggtcaaca tcgagcctgg caaactagcg    600 

ataacgttgt gttgaaaatc taagaaaagt ggaactccta tgtcacaacc tatttttaac    660 

gataagcaat ttcaggaagc gctttcacgt cagtggcagc gttatggctt aaattctgcg    720 

gctgaaatga ctcctcgcca gtggtggcta gcagtgagtg aagcactggc cgaaatgctg    780 

cgtgctcagc cattcgccaa gccggtggcg aatcagcgac atgttaacta catctcaatg    840 

gagtttttga ttggtcgcct gacgggcaac aacctgttga atctcggctg gtatcaggat    900 

gtacaggatt cgttgaaggc ttatgacatc aatctgacgg acctgctgga agaagagatc    960 

gacccggcgc tgggtaacgg tggtctggga cgtctggcgg cgtgcttcct cgactcaatg   1020 

gcaactgtcg gtcagtctgc gacgggttac ggtctgaact atcaatatgg tttgttccgc   1080 

cagtcttttg tcgatggcaa acaggttgaa gcgccggatg actggcatcg cagtaactac   1140 

ccgtggttcc gccacaacga agcactggat gtgcaggtag ggattggcgg taaagtgacg   1200 

aaagacggac gctgggagcc ggagtttacc attaccggtc aagcgtggga tctccccgtt   1260 

gtcggctatc gtaatggcgt ggcgcagccg ctgcgtctgt ggcaggcgac gcacgcgcat   1320 

ccgtttgatc tgactaaatt taacgacggt gatttcttgc gtgccgaaca gcagggcatc   1380 

aatgcggaaa aactgaccaa agttctctat ccaaacgaca accatactgc cggtaaaaag   1440 

ctgcgcctga tgcagcaata cttccagtgt gcctgttcgg tagcggatat tttgcgtcgc   1500 

catcatctgg cggggcgtga actgcacgaa ctggcggatt actaagttat tcagctgaac   1560 

gatacccacc caactatcgc gattccagaa ctgctgcgcg tgctgatcga tgagcaccag   1620 

atgagctggg atgacgcttg ggccattacc agcaaaactt tcgcttacac caaccatacc   1680 

ctgatgccag aagcgctgga acgctgggat gtgaaactgg tgaaaggctt actgccgcgc   1740 

cacatgcaga ttattaacga aattaatact cgctttaaaa cgctggtaga gaaaacctgg   1800 

ccgggcgatg aaaaagtgtg ggccaaactg gcggtggtgc acgacaaaca agtgcatatg   1860 

gcgaacctgt gtgtggttgg cggtttcgcg gtgaacggtg ttgcggcgct gcactcggat   1920 

ctggtggtga aagatctgtt cccggaatat caccagctat ggccgaacaa attccataac   1980 

gtcaccaacg gtattacccc acgtcgctgg atcaaacagt gcaacccggc actggcggct   2040 

ctgttggata aatcactgca aaaagagtgg gctaacgatc tcgatcagct gatcaatctg   2100 

gttaaattgg ctgatgatgc gaaattccgt cagctttatc gcgtgatcaa gcaggcgaat   2160 

aaagtccgtc tggcggagtt tgtgaaagtt cgtaccggta ttgacatcaa tccacaggcg   2220 

attttcgata ttcagatcaa acgtttgcac gagtacaaac gccagcacct gaatctgctg   2280 

cgtattctgg cgttgtacaa agaaattcgt gaaaacccgc aggctgatcg cgtaccgcgc   2340 

gtcttcctct tcggcgcgaa agcggcaccg ggctactacc tggctaagaa tattatcttt   2400 

gcgatcaaca aagtggctga cgtgatcaac aacgatccgc tggttggcga taagttgaag   2460 

gtggtgttcc tgccggatta ttgcgtttcg gcggcggaaa aactgatccc ggcggcggat   2520 

atctccgaac aaatttcgac tgcaggtaaa gaagcttccg gtaccggcaa tatgaaactg   2580 

gcgctcaatg gtgcgcttac tgtcggtacg ctggatgggg cgaacgttga aatcgccgag   2640 

aaagtcggtg aagaaaatat ctttattttt ggtcatacgg tcaaacaagt gaaggcaatc   2700 

gac                                                                 2703 

 
           
             7  
             1391  
             DNA  
             Escherichia coli  
           
            7 

agagaagcct gtcggcaccg tctggtttgc ttttgccact gcccgcggtg aaggcattac     60 

ccggcgggat gcttcagcgg cgaccgtgat gcggtgcgtc gtcaggctac tgcgtatgca    120 

ttgcagacct tgtggcaaca atttctacaa aacacttgat actgtatgag catacagtat    180 

aattgcttca acagaacata ttgactatcc ggtattaccc ggcatgacag gagtaaaaat    240 

ggctatcgac gaaaacaaac agaaagcgtt ggcggcagca ctgggccaga ttgagaaaca    300 

atttggtaaa ggctccatca tgcgcctggg tgaagaccgt tccatggatg tggaaaccat    360 

ctctaccggt tcgctttcac tggatatcgc gcttggggca ggtggtctgc cgatgggccg    420 

tatcgtcgaa atctacggac cggaatcttc cggtaaaacc acgctgacgc tgcaggtgat    480 

cgccgcagcg cagcgtgaag gtaaaacctg tgcgtttatc gatgctgaac acgcgctgga    540 

cccaatctac gcacgtaaac tgggcgtcga tatcgacaac ctgctgtgct cccagccgga    600 

caccggcgag caggcactgg aaatctgtga cgccctggcg cgttctggcg cagtagacgt    660 

tatcgtcgtt gactccgtgg cggcactgac gccgaaagcg gaaatcgaag gcgaaatcgg    720 

cgactctcac atgggccttg cggcacgtat gatgagccag gcgatgcgta agctggcggg    780 

taacctgaag cagtccaaca cgctgctgat cttcatcaac cagatccgta tgaaaattgg    840 

tgtgatgttc ggtaacccgg aaaccactac cggtggtaac gcgctgaaat tctacgcctc    900 

tgttcgtctc gacatccgtc gtatcggcgc ggtgaaagag ggcgaaaacg tggtgggtag    960 

cgaaacccgc gtgaaagtgg tgaagaacaa aatcgctgcg ccgtttaaac aggctgaatt   1020 

ccagatcctc tacggcgaag gtatcaactt ctacggcgaa ctggttgacc tgggcgtaaa   1080 

agagaagctg atcgagaaag caggcgcgtg gtacagctac aaaggtgaga agatcggtca   1140 

gggtaaagcg aatgcgactg cctggctgaa agataacccg gaaaccgcga aagagatcga   1200 

gaagaaagta cgtgagttgc tgctgagcaa cccgaactca acgccggatt tctctgtaga   1260 

tgatagcgaa ggcgtagcag aaactaacga agatttttaa tcgtcttgtt tgatacacaa   1320 

gggtcgcatc tgcggccctt ttgctttttt aagttgtaag gatatgccat gacagaatca   1380 

acatcccgtc g                                                        1391 

 
           
             8  
             238  
             DNA  
             Klebsiella pneumoniae  
           
            8 

tcgccaggaa ggcggcattc ggctgggtca gagtgacctg cagcgtggtg tcgttcagcg     60 

ctttcacccc caacgtctcg ggtccctttt gcccgagggc aatctcgcgg gcgttggcga    120 

tatgcatatt gccagggtag ctcgcgtagg gggaggctgt tgccggcgag accagccgtt    180 

gccagctcca gacgatatcc tgcgctgtaa tggccgtgcc gtcagaccag gtcagacc      238 

 
           
             9  
             385  
             DNA  
             Klebsiella pneumoniae  
           
            9 

cagcgtaatg cgccgcggca taacggcgcc actatcgaca gtcagttcgt cagcctgcag     60 

cctgggctga atctgggacc atggcgcctg ccgaactaca gcacctatag ccacagcgat    120 

aacaacagcc gctgggagtc ggtttactcc tatcttgccc gcgatattca caccctacgc    180 

agccagctgg tggtcggtaa tacgtatacc tcttccggca ttttcgacag tttgagtttt    240 

accggtctgc agctcagttc gacaaagaga tgctgccgga tagcctgcat gctttgcgcc    300 

gacgattcga gggatcgcgc gcaccaccgc ggaggtctcg gtttatcaga atggttacag    360 

catttataaa accaccgtcg ctacc                                          385 

 
           
             10  
             462  
             DNA  
             Klebsiella pneumoniae  
           
            10 

ctctatattc aggacgaaca tatctggacc tctggcgggg tcagttccgg ctttgatcgc     60 

cctgcacccg cagcgggtga tcgcccctca tctgctactg cggcgctgca acaggcgacg    120 

atcgatgacg ttattcctgg ccagcaaaca gcagaccaat taaggtctga tagtggctct    180 

cttcctccgg cgcgcgacgg tccaggcggc tcaacagttt ggtgcatagc gctttgcggt    240 

tgagatgacg cccttcgtta agaatatcca tcacgatctc cgtccatgga gagtagcgtt    300 

tattccagaa tagggttttt caggatctca tggatctgcg cctgcttatc gctattttgt    360 

aaccagatcg cataaagtgg acgggataac gtagcgctgt ccatgaccgt atgtaaccca    420 

tgcttctctt tcgcccagcg agcaggtagc caacagcagc cg                       462 

 
           
             11  
             730  
             DNA  
             Klebsiella pneumoniae  
           
            11 

gctgaccgct aaactgggtt acccgatcac tgacgatctg gacatctaca cccgtctggg     60 

cggcatggtt tggcgcgctg actccaaagg caactacgct tcaaccggcg tttcccgtag    120 

cgaacacgac actggcgttt ccccagtatt tgctggcggc gtagagtggg ctgttactcg    180 

tgacatcgct acccgtctgg aataccagtg ggttaacaac atcggcgacg cgggcactgt    240 

gggtacccgt cctgataacg gcatgctgag cctgggcgtt tcctaccgct tcggtcagga    300 

agatgctgca ccggttgttg ctccggctcc ggctccggct ccggaagtgg ctaccaagca    360 

cttcaccctg aagtctgacg ttctgttcaa cttcaacaaa gctaccctga aaccggaagg    420 

tcagcaggct ctggatcagc tgtacactca gctgagcaac atggatccga aagacggttc    480 

cgctgttgtt ctgggctaca ccgaccgcat cggttccgaa gcttacaacc agcagctgtc    540 

tgagaaacgt gctcagtccg ttgttgacta cctggttgct aaaggcatcc cggctggcaa    600 

aatctccgct cgcggcatgg gtgaatccaa cccggttact ggcaacacct gtgacaacgt    660 

gaaagctcgc gctgccctga tcgattgcct ggctccggat cgtcgtgtag agatcgaagt    720 

taaaggtatc                                                           730 

 
           
             12  
             225  
             DNA  
             Proteus mirabilis  
           
            12 

cgctactgtt taaatctcat ttgaaacatc gcaaagtcag tgaaccacat attcgaggat     60 

ggcatgcact agaaaatatt aataagattt tagcgaaacc taatcagcgc aatatcgctt    120 

aattatttta ggtatgttct cttctatcct acagtcacga ggcagtgtcg aacttgatcc    180 

tcattttatt aatcacatga ccaatggtat aagcgtcgtc acata                    225 

 
           
             13  
             402  
             DNA  
             Proteus mirabilis  
           
            13 

acattttaaa taggaagcca cctgataaca tccccgcagt tggatcatca gatttatagc     60 

ggcatttggt atccgctaga taaaagcagt ccaacgatcc cgccaattgt tagatgaaat    120 

tggactattc tttttatttg ctccgcttta tcacagtggt tttcgctttg ccgcccctgt    180 

gcgccaacag ctaagaacac gcacgctctt taatgtgtta ggcccattaa ttaatccagc    240 

gcgttccgcc tttagcatta attggtgttt atagtcctga attattaatg cctattgcag    300 

ataccttaaa tgtcttgggc tacaaacgtg cggcagtggt ccatagtggt ggaatggatg    360 

aagtgtcatt acatgctccc acacaagtgg ctgagttaca ca                       402 

 
           
             14  
             157  
             DNA  
             Proteus mirabilis  
           
            14 

ctgaaacgca tttatgcggg agtcagtgaa atcatcactc aattttcacc cgatgtattt     60 

tctgttgaac aagtctttat ggcaaaaaat gcagactcag cattaaaatt aggccaagca    120 

agaggtgtgg cgattttagc ggcagtcaat aatgatc                             157 

 
           
             15  
             1348  
             DNA  
             Proteus mirabilis  
           
            15 

tttctcttta aaatcaattc ttaaagaaat tattaataat taacttgata ctgtatgatt     60 

atacagtata atgagtttca acaagcaaaa tcatatacgt tttaatggta gtgacccatc    120 

tttatgcttc actgcccaga gggagataac atggctattg atgaaaacaa acaaaaagca    180 

ttggccgcag cacttggtca aattgaaaag caatttggta aaggttctat catgcgtctg    240 

ggcgaagacc gttccatgaa cgtagaaact atctctacag gatctttatc attagacgtt    300 

gctttaggtg caggtggatt gccacgtggc cgtattgttg aaatctatgg ccctgaatct    360 

tctggtaaaa caaccttgac tctacaagtt attgcctctg ctcagcgtga aggaaaaatt    420 

tgtgcattta ttgatgctga acatgcatta gacccaattt atgctcaaaa gctaggtgtc    480 

gatatcgata atctactctg ctctcaacct gacacaggtg aacaagctct ggaaatttgt    540 

gatgcattat ctcgctctgg tgcggtcgat gttattgtcg tggactccgt ggcagcatta    600 

acaccaaaag ctgaaattga aggtgaaatt ggtgattcac acgttggttt agccgcacgt    660 

atgatgagcc aagctatgcg taaactagcg ggtaacctta aaaactctaa tacactgctg    720 

attttcatta accaaattcg tatgaaaatc ggtgttatgt ttggtaaccc agaaaccacg    780 

accggtggta atgcgcttaa attctatgct tctgttcgtt tagacattcg tcgcattggc    840 

tctgtcaaaa atggtgatga agtcattggt agtgagactc gcgttaaagt tgttaaaaat    900 

aaagtggctg caccgtttaa acaagctgaa ttccaaatta tgtacggtga aggtattaat    960 

acctatggcg aactgattga tttaggtgtt aaacataagt tagtagagaa agcaggtgct   1020 

tggtatagct acaatggcga aaaaattggt caaggtaaag ctaacgcaac caattactta   1080 

aaagaacatc ctgaaatgta caatgagtta aacactaaat tgcgtgaaat gttgttaaat   1140 

catgctggtg aattcacaag tgctgcggat tttgcaggtg aagagtcaga cagtgatgct   1200 

gacgacacaa aagagtaatt agctggttgt catgctgttt gtgtgaaaat agaccttaaa   1260 

tcattggcta ttatcacgac agcatcccat agaataactt gtttgtataa attttattca   1320 

gatggcaaag gaagccttaa aaaagctt                                      1348 

 
           
             16  
             2167  
             DNA  
             Pseudomonas aeruginosa  
           
            16 

ggtaccgctg gccgagcatc tgctcgatca ccaccagccg ggcgacggga actgcacgat     60 

ctacctggcg agcctggagc acgagcgggt tcgcttcgta cggcgctgag cgacagtcac    120 

aggagaggaa acggatggga tcgcaccagg agcggccgct gatcggcctg ctgttctccg    180 

aaaccggcgt caccgccgat atcgagcgct cgcacgcgta tggcgcattg ctcgcggtcg    240 

agcaactgaa ccgcgagggc ggcgtcggcg gtcgcccgat cgaaacgctg tcccaggacc    300 

ccggcggcga cccggaccgc tatcggctgt gcgccgagga cttcattcgc aaccgggggg    360 

tacggttcct cgtgggctgc tacatgtcgc acacgcgcaa ggcggtgatg ccggtggtcg    420 

agcgcgccga cgcgctgctc tgctacccga ccccctacga gggcttcgag tattcgccga    480 

acatcgtcta cggcggtccg gcgccgaacc agaacagtgc gccgctggcg gcgtacctga    540 

ttcgccacta cggcgagcgg gtggtgttca tcggctcgga ctacatctat ccgcgggaaa    600 

gcaaccatgt gatgcgccac ctgtatcgcc agcacggcgg cacggtgctc gaggaaatct    660 

acattccgct gtatccctcc gacgacgact tgcagcgcgc cgtcgagcgc atctaccagg    720 

cgcgcgccga cgtggtcttc tccaccgtgg tgggcaccgg caccgccgag ctgtatcgcg    780 

ccatcgcccg tcgctacggc gacggcaggc ggccgccgat cgccagcctg accaccagcg    840 

aggcggaggt ggcgaagatg gagagtgacg tggcagaggg gcaggtggtg gtcgcgcctt    900 

acttctccag catcgatacg cccgccagcc gggccttcgt ccaggcctgc catggtttct    960 

tcccggagaa cgcgaccatc accgcctggg ccgaggcggc ctactggcag accttgttgc   1020 

tcggccgcgc cgcgcaggcc gcaggcaact ggcgggtgga agacgtgcag cggcacctgt   1080 

acgacatcga catcgacgcg ccacaggggc cggtccgggt ggagcgccag aacaaccaca   1140 

gccgcctgtc ttcgcgcatc gcggaaatcg atgcgcgcgg cgtgttccag gtccgctggc   1200 

agtcgcccga accgattcgc cccgaccctt atgtcgtcgt gcataacctc gacgactggt   1260 

ccgccagcat gggcggggga ccgctcccat gagcgccaac tcgctgctcg gcagcctgcg   1320 

cgagttgcag gtgctggtcc tcaacccgcc gggggaggtc agcgacgccc tggtcttgca   1380 

gctgatccgc atcggttgtt cggtgcgcca gtgctggccg ccgccggaag ccttcgacgt   1440 

gccggtggac gtggtcttca ccagcatttt ccagaatggc caccacgacg agatcgctgc   1500 

gctgctcgcc gccgggactc cgcgcactac cctggtggcg ctggtggagt acgaaagccc   1560 

cgcggtgctc tcgcagatca tcgagctgga gtgccacggc gtgatcaccc agccgctcga   1620 

tgcccaccgg gtgctgcctg tgctggtatc ggcgcggcgc atcagcgagg aaatggcgaa   1680 

gctgaagcag aagaccgagc agctccagga ccgcatcgcc ggccaggccc ggatcaacca   1740 

ggccaaggtg ttgctgatgc agcgccatgg ctgggacgag cgcgaggcgc accagcacct   1800 

gtcgcgggaa gcgatgaagc ggcgcgagcc gatcctgaag atcgctcagg agttgctggg   1860 

aaacgagccg tccgcctgag cgatccgggc cgaccagaac aataacaaga ggggtatcgt   1920 

catcatgctg ggactggttc tgctgtacgt tggcgcggtg ctgtttctca atgccgtctg   1980 

gttgctgggc aagatcagcg gtcgggaggt ggcggtgatc aacttcctgg tcggcgtgct   2040 

gagcgcctgc gtcgcgttct acctgatctt ttccgcagca gccgggcagg gctcgctgaa   2100 

ggccggagcg ctgaccctgc tattcgcttt tacctatctg tgggtggccg ccaaccagtt   2160 

cctcgag                                                             2167 

 
           
             17  
             1872  
             DNA  
             Pseudomonas aeruginosa  
           
            17 

gaattcccgg gagttcccga cgcagccacc cccaaaacac tgctaaggga gcgcctcgca     60 

gggctcctga ggagatagac catgccattt ggcaagccac tggtgggcac cttgctcgcc    120 

tcgctgacgc tgctgggcct ggccaccgct cacgccaagg acgacatgaa agccgccgag    180 

caataccagg gtgccgcttc cgccgtcgat cccgctcacg tggtgcgcac caacggcgct    240 

cccgacatga gtgaaagcga gttcaacgag gccaagcaga tctacttcca acgctgcgcc    300 

ggttgccacg gcgtcctgcg caagggcgcc accggcaagc cgctgacccc ggacatcacc    360 

cagcaacgcg gccagcaata cctggaagcg ctgatcacct acggcacccc gctgggcatg    420 

ccgaactggg gcagctccgg cgagctgagc aaggaacaga tcaccctgat ggccaagtac    480 

atccagcaca ccccgccgca accgccggag tggggcatgc cggagatgcg cgaatcgtgg    540 

aaggtgctgg tgaagccgga ggaccggccg aagaaacagc tcaacgacct cgacctgccc    600 

aacctgttct cggtgaccct gcgcgacgcc gggcagatcg ccctggtcga cggcgacagc    660 

aaaaagatcg tcaaggtcat cgataccggc tatgccgtgc atatctcgcg gatgtccgct    720 

tccggccgct acctgctggt gatcggccgc gacgcgcgga tcgacatgat cgacctgtgg    780 

gccaaggagc cgaccaaggt cgccgagatc aagatcggca tcgaggcgcg ctcggtggaa    840 

agctccaagt tcaagggcta cgaggaccgc tacaccatcg ccggcgccta ctggccgccg    900 

cagttcgcga tcatggacgg cgagaccctg gaaccgaagc agatcgtctc cacccgcggc    960 

atgaccgtag acacccagac ctaccacccg gaaccgcgcg tggcggcgat catcgcctcc   1020 

cacgagcacc ccgagttcat cgtcaacgtg aaggagaccg gcaaggtcct gctggtcaac   1080 

tacaaggata tcgacaacct caccgtcacc agcatcggtg cggcgccgtt cctccacgac   1140 

ggcggctggg acagcagcca ccgctacttc atgaccgccg ccaacaactc caacaaggtt   1200 

gccgtgatcg actccaagga ccgtcgcctg tcggccctgg tcgacgtcgg caagaccccg   1260 

cacccggggc gtggcgccaa cttcgtgcat cccaagtacg gcccggtgtg gagcaccagc   1320 

cacctgggcg acggcagcat ctcgctgatc ggcaccgatc cgaagaacca tccgcagtac   1380 

gcctggaaga aagtcgccga actacagggc cagggcggcg gctcgctgtt catcaagacc   1440 

catccgaagt cctcgcacct ctacgtcgac accaccttca accccgacgc caggatcagc   1500 

cagagcgtcg cggtgttcga cctgaagaac ctcgacgcca agtaccaggt gctgccgatc   1560 

gccgaatggg ccgatctcgg cgaaggcgcc aagcgggtgg tgcagcccga gtacaacaag   1620 

cgcggcgatg aagtctggtt ctcggtgtgg aacggcaaga acgacagctc cgcgctggtg   1680 

gtggtggacg acaagaccct gaagctcaag gccgtggtca aggacccgcg gctgatcacc   1740 

ccgaccggta agttcaacgt ctacaacacc cagcacgacg tgtactgaga cccgcgtgcg   1800 

gggcacgccc cgcacgctcc cccctacgag gaaccgtgat gaaaccgtac gcactgcttt   1860 

cgctgctcgc ca                                                       1872 

 
           
             18  
             3451  
             DNA  
             Pseudomonas aeruginosa  
           
            18 

tcgagacggg aagccactct ctacgagaag acagaagccc ctcacagagg cctctgtcta     60 

cgcctactaa agctcggctt attcatatgt atttatattc tttcaataga tcactcagcg    120 

ctattttaag ttcaccctct gtaagttcac ctgggcgctc tttctttcct tcggtaaagc    180 

tgtcggccag accaaacatt aaactcaagc atctcccaag cgatgcatca tcttgggcca    240 

gcatccctga atcgcgcgtc ggacctccaa gtcttaaaaa attcttcgct gaaggttttc    300 

ccatcaatcg atgaggctaa tagcttcttt gcaatatcta tcatttccat gctcacctta    360 

aagcacctca tttttcatgt aaaaattgta ttgatccgtg ccagactcaa tcctccaccc    420 

agaaacaaac atcccatcct ctccaatgat aacaacaata ttagtcctgg cattgtaatg    480 

tacttttgag tttacttcgg agtggtaagt ccctttttct acggttgcag gatcagcaag    540 

gtgctcaaga attttatccc taaactctgc aagcgttcca ttgttggcgc ttttttcacc    600 

cagcccaaaa tcatatttgt ggctatcaaa ttttttctgt agttgcctcc gtgtgaagat    660 

accactatca agaggactac tgagcattac ataaacaggt ttgactccag aatccgccgg    720 

gaaaatcacg atcagatcgt ttaggtccag tagcattccc ggataggact ccgggccggt    780 

cttcaacggt gtgagggccg ctccctcata taccggcacc ggcttcggta tgaccggagt    840 

ggtactcgaa gggttctggt ttcctggagg actcgccggc gtccaagtca ggatcagtgg    900 

cggcgcttct gcgaccgtag agggaaccgt aacctcgtac agtcctgttg cggcgttata    960 

ggccccatcc ggaccggaac gctttcggaa cgctcacacc atcggtctga ccaccgaaag   1020 

gtcgtcgtgt tgcctcgcgc ctcgttggtc aggcgcatcg gcagatcgac ggtaccgctg   1080 

gcttttgcaa ccgcgttcag gtttacgctt gggggaagcc ccaatttagc ggcatccatg   1140 

cccagggcgt aacgaacgct atcgggcgtt tggtcctgcc attgctcggc agtccgggag   1200 

agtaggtcag actggcaagc cacggccatc accgaggtgc tgaagccagg accgccagga   1260 

cggcaatcgc atcggagatc gcttgagcaa gggatgcggc gcctgtgcga cctggatcag   1320 

accccgctgc ggcggtggcg cacccgctgc cattggctgg catggcataa gtattggcag   1380 

ccctgatcgc cgcttgacga gcgatttcct tgcgccttgc cgtttcggcg ttcagcttgt   1440 

ccagccgtgc ttgcaggctg gcgatttcat ccactaggta ggacatcggc gttgtaggtt   1500 

gccttttgtt tctccagtgc attgggtgcc ttggcaatca aggcattgtt tgcagtctgc   1560 

aattcttctt attgcgatcg cctgcgtaag gagttgagta gcgcgttcaa gccactgctc   1620 

tggcgttgga ttggtcagtt gaggcaaagc attcccagcc tggtcaagct cggactgcac   1680 

ttttttctcg acatttgcct tcctggcctt gtagtccgcc tccacctcag cagcggctcg   1740 

ctgggcttct gcttccaatg accgggcttt attctccagc tcttgagacg tttgtttcaa   1800 

gatagcgatt tgcgccttat agatatcggc gctgtacgct ttggccagct cactcatatg   1860 

gcgatccagg aactctccat agaattttcg gctggccagc aactgactct ggtacatcga   1920 

ctctgacttc tgaggaaagt ctgaagccgt ataaagattg gccgggcgat cctcaatgac   1980 

ctttagcgat tttgctttgg catccatgag tgcatcaacg atactctttt catcgcggat   2040 

gtcattggca ctgaccgctt tacctggcaa ccccgcttca ctcttgagtt catcaacctc   2100 

cttcagggtt tcatttttca ggtttttctt gagttctgaa tgggacttat caagcgtact   2160 

tcttagcttc ctgtactcct gcattccagt accgacatac ggacttggtc ctggtgggac   2220 

aaatggtgga gtaccgtagc ttgatcgagc aggaatatac tggattatgt cacgcccacc   2280 

accctgcaca tgtgtaataa ccatcgaacc aggttcgtaa tcattgacag ccatagatcg   2340 

cccctacatt aatttgaaag tgtaatgtat tgagcgactc ccacctagag aaccctctcc   2400 

cagtcaataa gccccaatgc atcggcaata cactgcaatc aacttcaata tcccgtgttt   2460 

agatgatcca gaaggtgcgc tctctcgcct cttataatcg cgcctgcgtc aaacggtcat   2520 

ttccttaacg cacacctcat ctaccccggc cagtcacgga agccgcatac cttcggttca   2580 

ttaacgaact cccactttca aaattcatcc atgccgcccc ttcgcgagct tccggacaaa   2640 

gccacgctga ttgcgagccc agcgtttttg attgcaagcc gctgcagctg gtcaggccgt   2700 

ttccgcaacg cttgaagtcc tggccgatat accggcaggg ccagccatcg ttcgacgaat   2760 

aaagccacct cagccatgat gccctttcca tccccagcgg aaccccgaca tggacgccaa   2820 

agccctgctc ctcggcagcc tctgcctggc cgccccattc gccgacgcgg cgacgctcga   2880 

caatgctctc tccgcctgcc tcgccgcccg gctcggtgca ccgcacacgg cggagggcca   2940 

gttgcacctg ccactcaccc ttgaggcccg gcgctccacc ggcgaatgcg gctgtacctc   3000 

ggcgctggtg cgatatcggc tgctggccag gggcgccagc gccgacagcc tcgtgcttca   3060 

agagggctgc tcgatagtcg ccaggacacg ccgcgcacgc tgaccctggc ggcggacgcc   3120 

ggcttggcga gcggccgcga actggtcgtc accctgggtt gtcaggcgcc tgactgacag   3180 

gccgggctgc caccaccagg ccgagatgga cgccctgcat gtatcctccg atcggcaagc   3240 

ctcccgttcg cacattcacc actctgcaat ccagttcata aatcccataa aagccctctt   3300 

ccgctccccg ccagcctccc cgcatcccgc accctagacg ccccgccgct ctccgccggc   3360 

tcgcccgaca agaaaaacca accgctcgat cagcctcatc cttcacccat cacaggagcc   3420 

atcgcgatgc acctgatacc ccattggatc c                                  3451 

 
           
             19  
             744  
             DNA  
             Pseudomonas aeruginosa  
           
            19 

gggttcagca agcgttcagg ggcggttcag taccctgtcc gtactctgca agccgtgaac     60 

gacacgactc tcgcagaacg gagaaacacc atgaaagcac tcaagactct cttcatcgcc    120 

accgccctgc tgggttccgc cgccggcgtc caggccgccg acaacttcgt cggcctgacc    180 

tggggcgaga ccagcaacaa catccagaaa tccaagtcgc tgaaccgcaa cctgaacagc    240 

ccgaacctcg acaaggtgat cgacaacacc ggcacctggg gcatccgcgc cggccagcag    300 

ttcgagcagg gccgctacta cgcgacctac gagaacatct ccgacaccag cagcggcaac    360 

aagctgcgcc agcagaacct gctcggcagc tacgacgcct tcctgccgat cggcgacaac    420 

aacaccaagc tgttcggcgg tgccaccctc ggcctggtca agctggaaca ggacggcaag    480 

ggcttcaagc gcgacagcga tgtcggctac gctgccgggc tgcaggccgg tatcctgcag    540 

gagctgagca agaatgcctc gatcgaaggc ggctatcgtt acctgcgcac caacgccagc    600 

accgagatga ccccgcatgg cggcaacaag ctgggctccc tggacctgca cagcagctcg    660 

caattctacc tgggcgccaa ctacaagttc taaatgaccg cgcagcgccc gcgagggcat    720 

gcttcgatgg ccgggccgga aggt                                           744 

 
           
             20  
             2760  
             DNA  
             Pseudomonas aeruginosa  
           
            20 

ctgcagctgg tcaggccgtt tccgcaacgc ttgaagtcct ggccgatata ccggcagggc     60 

cagccatcgt tcgacgaata aagccacctc agccatgatg ccctttccat ccccagcgga    120 

accccgacat ggacgccaaa gccctgctcc tcggcagcct ctgcctggcc gccccattcg    180 

ccgacgcggc gacgctcgac aatgctctct ccgcctgcct cgccgcccgg ctcggtgcac    240 

cgcacacggc ggagggccag ttgcacctgc cactcaccct tgaggcccgg cgctccaccg    300 

gcgaatgcgg ctgtacctcg gcgctggtgc gatatcggct gctggccagg ggcgccagcg    360 

ccgacagcct cgtgcttcaa gagggctgct cgatagtcgc caggacacgc cgcgcacgct    420 

gaccctggcg gcggacgccg gcttggcgag cggccgcgaa ctggtcgtca ccctgggttg    480 

tcaggcgcct gactgacagg ccgggctgcc accaccaggc cgagatggac gccctgcatg    540 

tatcctccga tcggcaagcc tcccgttcgc acattcacca ctctgcaatc cagttcataa    600 

atcccataaa agccctcttc cgctccccgc cagcctcccc gcatcccgca ccctagacgc    660 

cccgccgctc tccgccggct cgcccgacaa gaaaaaccaa ccgctcgatc agcctcatcc    720 

ttcacccatc acaggagcca tcgcgatgca cctgataccc cattggatcc ccctggtcgc    780 

cagcctcggc ctgctcgccg gcggctcgtc cgcgtccgcc gccgaggaag ccttcgacct    840 

ctggaacgaa tgcgccaaag cctgcgtgct cgacctcaag gacggcgtgc gttccagccg    900 

catgagcgtc gacccggcca tcgccgacac caacggccag ggcgtgctgc actactccat    960 

ggtcctggag ggcggcaacg acgcgctcaa gctggccatc gacaacgccc tcagcatcac   1020 

cagcgacggc ctgaccatcc gcctcgaagg cggcgtcgag ccgaacaagc cggtgcgcta   1080 

cagctacacg cgccaggcgc gcggcagttg gtcgctgaac tggctggtac cgatcggcca   1140 

cgagaagccc tcgaacatca aggtgttcat ccacgaactg aacgccggca accagctcag   1200 

ccacatgtcg ccgatctaca ccatcgagat gggcgacgag ttgctggcga agctggcgcg   1260 

cgatgccacc ttcttcgtca gggcgcacga gagcaacgag atgcagccga cgctcgccat   1320 

cagccatgcc ggggtcagcg tggtcatggc ccagacccag ccgcgccggg aaaagcgctg   1380 

gagcgaatgg gccagcggca aggtgttgtg cctgctcgac ccgctggacg gggtctacaa   1440 

ctacctcgcc cagcaacgct gcaacctcga cgatacctgg gaaggcaaga tctaccgggt   1500 

gctcgccggc aacccggcga agcatgacct ggacatcaaa cccacggtca tcagtcatcg   1560 

cctgcacttt cccgagggcg gcagcctggc cgcgctgacc gcgcaccagg cttgccacct   1620 

gccgctggag actttcaccc gtcatcgcca gccgcgcggc tgggaacaac tggagcagtg   1680 

cggctatccg gtgcagcggc tggtcgccct ctacctggcg gcgcggctgt cgtggaacca   1740 

ggtcgaccag gtgatccgca acgccctggc cagccccggc agcggcggcg acctgggcga   1800 

agcgatccgc gagcagccgg agcaggcccg tctggccctg accctggccg ccgccgagag   1860 

cgagcgcttc gtccggcagg gcaccggcaa cgacgaggcc ggcgcggcca acgccgacgt   1920 

ggtgagcctg acctgcccgg tcgccgccgg tgaatgcgcg ggcccggcgg acagcggcga   1980 

cgccctgctg gagcgcaact atcccactgg cgcggagttc ctcggcgacg gcggcgacgt   2040 

cagcttcagc acccgcggca cgcagaactg gacggtggag cggctgctcc aggcgcaccg   2100 

ccaactggag gagcgcggct atgtgttcgt cggctaccac ggcaccttcc tcgaagcggc   2160 

gcaaagcatc gtcttcggcg gggtgcgcgc gcgcagccag gacctcgacg cgatctggcg   2220 

cggtttctat atcgccggcg atccggcgct ggcctacggc tacgcccagg accaggaacc   2280 

cgacgcacgc ggccggatcc gcaacggtgc cctgctgcgg gtctatgtgc cgcgctcgag   2340 

cctgccgggc ttctaccgca ccagcctgac cctggccgcg ccggaggcgg cgggcgaggt   2400 

cgaacggctg atcggccatc cgctgccgct gcgcctggac gccatcaccg gccccgagga   2460 

ggaaggcggg cgcctggaga ccattctcgg ctggccgctg gccgagcgca ccgtggtgat   2520 

tccctcggcg atccccaccg acccgcgcaa cgtcggcggc gacctcgacc cgtccagcat   2580 

ccccgacaag gaacaggcga tcagcgccct gccggactac gccagccagc ccggcaaacc   2640 

gccgcgcgag gacctgaagt aactgccgcg accggccggc tcccttcgca ggagccggcc   2700 

ttctcggggc ctggccatac atcaggtttt cctgatgcca gcccaatcga atatgaattc   2760 

 
           
             21  
             172  
             DNA  
             Staphylococcus saprophyticus  
           
            21 

ttgatgaaat gcatcgatta ataaattttc atgtacgatt aaaacgtttt tacccttacc     60 

ttttcgtact acctctgcct gaagttgacc acctttaaag tgattcgttg aaatccatta    120 

tgctcattat taatacgatc tataaaaaca aatggaatgt gatgatcgat ga            172 

 
           
             22  
             155  
             DNA  
             Staphylococcus saprophyticus  
           
            22 

gttccattga ctctgtatca cctgttgtaa cgaacatcca tatgtcctga aactccaacc     60 

acaggtttga ccacttccaa tttcagacca ccaagtttga cacgtgaaga ttcatcttct    120 

aatatttcgg aattaatatc atattattta aatag                               155 

 
           
             23  
             145  
             DNA  
             Staphylococcus saprophyticus  
           
            23 

acatagaaaa actcaaaaga tttacttttt tcaaatggaa aataagggta cacacgatat     60 

ttcccgtcat cttcagttac cggtacaaca tcctctttat taacctgcac ataatctgac    120 

tccgcttcac tcatcaaact actaa                                          145 

 
           
             24  
             266  
             DNA  
             Staphylococcus saprophyticus  
           
            24 

tttcactgga attacatttc gctcattacg tacagtgaca atcgcgtcag atagtttctt     60 

ctggttagct tgactcttaa caatcttgtc taaattttgt ttaattcttt gattcgtact    120 

agaaatttta cttctaattc cttgtaattc ataacttgca ttatcatata aatcataagt    180 

atcacatttt tgatgaatac tttgatataa atctgacaat acaggcagtt gctccattct    240 

atcgttaaga atagggtaat taatag                                         266 

 
           
             25  
             845  
             DNA  
             Haemophilus influenzae  
           
            25 

tgttaaattt ctttaacagg gattttgtta tttaaattaa acctattatt ttgtcgcttc     60 

tttcactgca tctactgctt gagttgcttt ttctgaaacc gcctctttca tttcacttgc    120 

tttttctgat gctgcttctt tcatttcgcc tactttttct gacgctgctt ctgttgctga    180 

tttaattact tctttcgcat cttccacttt ctctgctact ttatttttca cgtctgtaga    240 

aagctgctgt gctttttcct ttacttcagt cattgtatta gctgcagcat cttttgtttc    300 

tgatgcgact gatgctacag tttgcttcgt atcctcaact ttttgttttg cttcttgctt    360 

atcaaaacaa cctgtcacga ctaaagctga acctaaaacc aatgctaatg ttaatttttt    420 

cattattttc tccatagaat aatttgattg ttacaaagcc ctattacttt gatgcagttt    480 

agtttacggg aattttcata aaaagaaaaa cagtaatagt aaaactttac ctttctttaa    540 

aaagattact ttataaaaaa acatctaaga tattgatttt taatagatta taaaaaacca    600 

ataaaaattt tattttttgt aaaaaaaaag aatagtttat tttaaataaa ttacaggaga    660 

tgcttgatgc atcaatattt ctgatttatt accatcccat aataattgag caatagttgc    720 

aggataaaat gatattggat ttcgttttcc atacagttca gcaacaattt ctcccactaa    780 

gggcaaatgg gaaacaatta atacagattt aacgccctcg tcttttagca cttctaaata    840 

atcaa                                                                845 

 
           
             26  
             1598  
             DNA  
             Haemophilus influenzae  
           
            26 

gaatagagtt gcactcaata gattcgggct ttataattgc ccagattttt atttataaca     60 

aagggttcca aatgaaaaaa tttaatcaat ctctattagc aactgcaatg ttgttggctg    120 

caggtggtgc aaatgcggca gcgtttcaat tggcggaagt ttctacttca ggtcttggtc    180 

gtgcctatgc gggtgaagcg gcgattgcag ataatgcttc tgtcgtggca actaacccag    240 

ctttgatgag tttatttaaa acggcacagt tttccacagg tggcgtttat attgattcta    300 

gaattaatat gaatggtgat gtaacttctt atgctcagat aataacaaat cagattggaa    360 

tgaaagcaat aaaggacggc tcagcttcac agcgtaatgt tgttcccggt gcttttgtgc    420 

caaatcttta tttcgttgcg ccagtgaatg ataaattcgc gctgggtgct ggaatgaatg    480 

tcaatttcgg tctaaaaagt gaatatgacg atagttatga tgctggtgta tttggtggaa    540 

aaactgactt gagtgctatc aacttaaatt taagtggtgc ttatcgagta acagaaggtt    600 

tgagcctagg tttaggggta aatgcggttt atgctaaagc ccaagttgaa cggaatgctg    660 

gtcttattgc ggatagtgtt aaggataacc aaataacaag cgcactctca acacagcaag    720 

aaccattcag agatcttaag aagtatttgc cctctaagga caaatctgtt gtgtcattac    780 

aagatagagc cgcttggggc tttggctgga atgcaggtgt aatgtatcaa tttaatgaag    840 

ctaacagaat tggtttagcc tatcattcta aagtggacat tgattttgct gaccgcactg    900 

ctactagttt agaagcaaat gtcatcaaag aaggtaaaaa aggtaattta acctttacat    960 

tgccagatta cttagaactt tctggtttcc atcaattaac tgacaaactt gcagtgcatt   1020 

atagttataa atatacccat tggagtcgtt taacaaaatt acatgccagc ttcgaagatg   1080 

gtaaaaaagc ttttgataaa gaattacaat acagtaataa ctctcgtgtt gcattagggg   1140 

caagttataa tctttatgaa aaattgacct tacgtgcggg tattgcttac gatcaagcgg   1200 

catctcgtca tcaccgtagt gctgcaattc cagataccga tcgcacttgg tatagtttag   1260 

gtgcaaccta taaattcacg ccgaatttat ctgttgatct tggctatgct tacttaaaag   1320 

gcaaaaaagt tcactttaaa gaagtaaaaa caataggtga caaacgtaca ttgacattga   1380 

atacaactgc aaattatact tctcaagcac acgcaaatct ttacggtttg aatttaaatt   1440 

atagtttcta atccgttaaa aaatttagca taataaagca caattccaca ctaagtgtgc   1500 

ttttctttta taaaacaagg cgaaaaatga ccgcacttta ttacacttat tacccctcgc   1560 

cagtcggacg gcttttgatt ttatctgacg gcgaaaca                           1598 

 
           
             27  
             9100  
             DNA  
             Haemophilus influenzae  
           
            27 

gtcaaaaatt gcgtgcattc tagcgaaaaa atgggctttt gggaactgtg ggatttattt     60 

aaaatcttag aaaatcttac cgcactttta agctataaag tgcggtgaaa tttagtggcg    120 

tttataatgg agaattactc tggtgtaatc cattcgactg tccagcttcc agtaccttct    180 

ggaactaatg tttttgtgag ataaggcaaa atttctttca tttgggtttc taatgtccaa    240 

ggtggattaa ttaccaccat accgctcgca gtcattcctc gttgatcgct atctgggcga    300 

acggcgagtt caatttttag aatttttcta attcccgttg cttctaaacc cttaaaaata    360 

cgtttagttt gttggcgtaa tacaacagga taccaaatcg cataagtgcc agtggcaaaa    420 

cgtttatagc cctcttcaat ggctttaaca acgagatcat aatcatcttt taattcataa    480 

ggcggatcga tgagtactaa gcctcggcgt tcttttggcg gaagcgttgc tttgacttgt    540 

tgaaagccat tgtcacattt tacggtgaca tttttgtcgt cgctaaaatt attgcgaaga    600 

attggataat cgctaggatg aagctcggtc aatagtgcgc gatcttgtga gcgcaacaat    660 

tccgcggcaa ttaatggaga acccgcgtaa taacgtagtt ctttgccacc ataattgagt    720 

tttttgatca tttttacata acgagcaata tcttcgggta aatctgtttg atcccacagg    780 

cgtccaatac cttctttata ttcccccgtt ttttctgatt catttgagga taaacgataa    840 

cgccccacac cagagtgcgt atccaaataa aaaaagcctt tttctttgag tttaagattt    900 

tccaaaatga gcattaaaac aatatgtttc aagacatcgg catgattgcc agcgtgaaat    960 

gagtgatgat aactcagcat aatatattcc ttatatattc cttatttgtt taataacgaa   1020 

ggcgagccaa ttgactcgcc cgattacaca ctaaagtgcg gtcattttta gaagagttct   1080 

tgtggttgcg tcgctggcgt attgccttca ttatttaagc gttgctgtaa ctcagtagga   1140 

acataataac cacgctcttg catttccgaa agataggtac gtgtcggttc tgttcccgca   1200 

ataaaatatt ctttgcgccc accgtttgga gaaagcaaac ctgtcaaagt atcaatgttt   1260 

ttttccacaa tttttggcgg tagcgacaat ttacgttctg gcttatcact caaagccgtt   1320 

ttcatataag tgatccaagc aggcattgct gtttttgctc ctgcttctcc acgcccaagt   1380 

actcgtttgt tatcatcaaa cccgacataa gttgtggtta ctaagtttgc accaaatccc   1440 

gcataccaag ccacttttga actgttggta gtacctgttt taccgcctat atcgctacgt   1500 

ttaatgcttt gtgcaatacg ccagctggtg cctttccagt ctaaaccttg ttcgccataa   1560 

attgccgtat ttaaggcact acgaatgaga aaagcaagtt cgccactaat gacacgtggc   1620 

gcatattcta ttttcgacga agcatttttt gcagcagcca ttaaatcaat cgcatcttct   1680 

ttaagtgcgg tcatatttga ttgtaattct ggcagttcag gcacagtttc aggttgttga   1740 

tctaattctt cgccattggt gctgtcatct gttggtttta aggcattctc gcctaaagga   1800 

atattggcaa agccgttgat tttgtctttg gtttcgccat aaattacagg tatatcatta   1860 

cattcaatgc aagcaatttt agggtttgca ataaataagt ctttacccgt gttatcttga   1920 

attttttcaa tgatataagg ttcaatgagg aagccaccat tatcaaacac cgcataagct   1980 

cgcgccattt ctaatggtgt gaaagaggct gcgccaagtg ctaaggcttc actggcaaaa   2040 

tattgatcac gtttaaaacc aaaacgttgt aaaaattctg ctgtgaaatc aatacctgcc   2100 

gtttggatag cacgaatagc aattatattt ttggattgac ctaatcctac gcgtaaacgc   2160 

atcgggccat cataacgatc aggcgagttt ttcggttgcc acattttttg tcccggtttt   2220 

tgaatagaaa tcgggctgtc ttgtaatacg cttgaaagtg ttaagccttt ttctaatgct   2280 

gccgcgtaaa taaatggttt gatagaagaa cccacttgaa ctaaagactg tgtggctcga   2340 

ttgaatttac tttgttcata gctaaagcca ccgaccactg cttcaatcgc accattatct   2400 

gaattaagag aaactaatgc tgaatttgct gcgggaattt gtcctaattg ccattcccca   2460 

ttagcacgct gatgaatcca aatttgctcg ccgactttca caggattgct tctgcctgtc   2520 

caacgcattg cattggttga taaggtcatt ttttccccag aagcgagcaa tatatcagca   2580 

ccgcctttta caattccaat cactgccgca ggaataaatg gctctgaatc aggtagtttg   2640 

cgtagaaaac cgacaatgcg atcattgtcc caagcggctt catttttttg ccataatggc   2700 

gcgccaccgc gataaccgtg acgcatatcg taatcaatca agttattacg cacagctttt   2760 

tgggcttcag cttggtcttt tgaaagtaca gtggtaaata ctttataacc actggtgtaa   2820 

gcattttctt cgccaaaacg acgcaccatt tcttgacgca ccatttcagt gacataatcg   2880 

gctcgaaatt caaattttgc gccgtgatag ctcgccacaa tcggctcttt caatgcagca   2940 

tcatattctt ctttgctgat gtatttttca tctaacatac ggcttagcac cacattgcgg   3000 

cgttcttctg aacgttttaa agaataaagc gggttcattg ttgaaggtgc tttaggtaaa   3060 

ccagcaataa tcgccatttc cgataaggtc aattcattca atgatttacc gaaataggtt   3120 

tgtgctgccg ctgcaacacc ataagaacga tagcctaaaa agattttgtt taaataaagc   3180 

tctaatattt cttgtttgtt gagagtattt tcgatttcta ccgcaagcac ggcttcacga   3240 

gctttacgaa taatggtttt ttctgaggtt aagaaaaagt tacgcgctaa ttgttgagta   3300 

atcgtacttg cgccttgtga tgcaccgcca ttactcactg cgacaaacaa tgcacgggca   3360 

atgccgatag ggtctaatcc gtgatgatcg taaaaacgac tgtcttccgt cgctaaaaat   3420 

gcgtcaatta agcgttgtgg cacatcggct aatttcactg gaatacggcg ttgctcaccc   3480 

acttcgccaa ttaatttacc gtcagccgta taaatctgca ttggttgctg taattcaacg   3540 

gtttttaatg tttctactga gggcaattca gattttaagt ggaaatacaa cattccgcct   3600 

gctactaaac ctaaaataca taaagttaat agggtgttta atattaattt tgcgatccgc   3660 

atcgtaaaat tctcgcttcg ttaatgaata ttcttgtcaa gagacctatg atttggctgt   3720 

taagtataaa agattcagcc tttaaagaat aggaaagaat atgcaattct ccctgaaaaa   3780 

ttaccgcact ttacaaatcg gcattcatcg taagcagagt tattttgatt ttgtgtggtt   3840 

tgatgatctc gaacagccac aaagttatca aatctttgtt aatgatcgtt attttaaaaa   3900 

tcgtttttta caacagctaa aaacacaata tcaagggaaa acctttcctt tgcagtttgt   3960 

agcaagcatt cccgcccact taacttggtc gaaagtatta atgttgccac aagtgttaaa   4020 

tgcgcaagaa tgtcatcaac aatgtaaatt tgtgattgaa aaagagctgc ctattttttt   4080 

agaagaattg tggtttgatt atcgttctac cccgttaaag caaggttttc gattagaggt   4140 

tactgcaatt cgtaaaagta gcgctcaaac ttatttgcaa gattttcagc catttaatat   4200 

taatatattg gatgttgcgt caaatgctgt tttgcgtgca tttcaatatc tgttgaatga   4260 

acaagtgcgg tcagaaaata ccttattttt atttcaagaa gatgactatt gcttggcgat   4320 

ttgtgaaaga tctcagcaat cacaaatttt acaatctcac gaaaatttga ccgcacttta   4380 

tgaacaattt accgaacgtt ttgaaggaca acttgaacaa gtttttgttt atcaaattcc   4440 

ctcaagtcat acaccattac ccgaaaactg gcagcgagta gaaacagaac tcccttttat   4500 

tgcgctgggc aacgcgctat ggcaaaaaga tttacatcaa caaaaagtgg gtggttaaat   4560 

gtcgatgaat ttattgcctt ggcgtactta tcaacatcaa aagcgtttac gtcgtttagc   4620 

tttttatatc gctttattta tcttgcttgc tattaattta atgttggctt ttagcaattt   4680 

gattgaacaa cagaaacaaa atttgcaggc acagcaaaag tcgtttgaac aacttaatca   4740 

acagcttcat aaaactacca tgcaaattga tcagttacgc attgcggtga aagttggtga   4800 

agttttgaca tctattccca acgagcaagt aaaaaagagt ttacaacagc taagtgaatt   4860 

accttttcaa caaggagaac tgaataaatt taaacaagat gccaataact taagcttgga   4920 

aggtaacgcg caagatcaaa cagaatttga actgattcat caatttttaa agaaacattt   4980 

tcccaatgtg aaattaagtc aggttcaacc tgaacaagat acattgtttt ttcactttga   5040 

tgtggaacaa ggggcggaaa aatgaaagct ttttttaacg atccttttac tccttttgga   5100 

aaatggctaa gtcagccttt ttatgtgcac ggtttaacct ttttattgct attaagtgcg   5160 

gtgatttttc gccccgtttt agattatata gaggggagtt cacgtttcca tgaaattgaa   5220 

aatgagttag cggtgaaacg ttcagaattg ttgcatcaac agaaaatttt aacctcttta   5280 

caacagcagt cggaaagtcg aaaactttct ccagaactgg ctgcacaaat tattcctttg   5340 

aataaacaaa ttcaacgttt agctgcgcgt aacggtttat ctcagcattt acgttgggaa   5400 

atggggcaaa agcctatttt gcatttacag cttacaggtc attttgaaaa aacgaagaca   5460 

tttttatccg cacttttggc taattcgtca cagctttctg taagtcggtt gcaatttatg   5520 

aaacccgaag acggcccatt gcaaaccgag atcatttttc agctagataa ggaaacaaaa   5580 

tgaaacattg gtttttcctg attatattat tttttatgaa ttgcagttgg ggacaagatc   5640 

ctttcgataa aacacagcgt aaccgttctc agtttgataa cgcacaaaca gtaatggagc   5700 

aaacagaaat aatttcctca gatgtgccta ataatctatg cggagcggat gaaaatcgcc   5760 

aagcggctga aattcctttg aacgctttaa aattggtggg ggtagtgatt tctaaagata   5820 

aagcctttgc cttgttgcaa gatcaaggtt tgcaagttta cagcgtttta gagggcgttg   5880 

atgtggctca agagggctat attgtagaaa aaatcaacca aaacaatgtt caatttatgc   5940 

gtaagctagg agagcaatgt gatagtagtg aatggaaaaa attaagtttt taaaggaaga   6000 

ttatgaagaa atatttttta aagtgcggtt attttttagt atgtttttgt ttgccattaa   6060 

tcgtttttgc taatcctaaa acagataacg aacgtttttt tattcgttta tcgcaagcac   6120 

ctttagctca aacactggag caattagctt ttcaacaaga tgtgaattta gtgattggag   6180 

atatattgga aaacaagatc tctttgaaat taaacaatat tgatatgcca cgtttgctac   6240 

aaataatcgc aaaaagtaag catcttactt tgaataaaga tgatgggatt tattatttaa   6300 

acggcagtca atctggcaaa ggtcaggttg caggaaatct tacgacaaat gaaccgcact   6360 

tagtgagtca cacggtaaaa ctccattttg ctaaagcttc tgaattaatg aaatccttaa   6420 

caacaggaag tggctctttg ctttctcccg ctgggagcat tacctttgat gatcgcagta   6480 

atttgctggt tattcaggat gaacctcgtt ctgtgcaaaa tatcaaaaaa ctgattgctg   6540 

aaatggataa gcctattgaa cagatcgcta ttgaagcgcg aattgtgaca attacggatg   6600 

agagtttgaa agaacttggc gttcggtggg ggatttttaa tccaactgaa aatgcaagac   6660 

gagttgcggg cagccttaca ggcaatagct ttgaaaatat tgcggataat cttaatgtaa   6720 

attttgcgac aacgacgaca cctgctggct ctatagcatt acaagtcgcc aaaattaatg   6780 

ggcgattgct tgatttagaa ttgagtgcgt tggagcgtga aaataatgta gaaattattg   6840 

caagccctcg cttactcact accaataaga aaagtgcgag cattaaacag gggacagaaa   6900 

ttccttacat cgtgagtaat actcgtaacg atacgcaatc tgtggaattt cgtgaggcgg   6960 

tgcttggttt ggaagtgacg ccacatattt ctaaagataa caatatctta cttgatttat   7020 

tggtaagtca aaattcccct ggttctcgtg tcgcttatgg acaaaatgag gtggtttcta   7080 

ttgataaaca agaaattaat actcaggttt ttgccaaaga tggggaaacc attgtgcttg   7140 

gcggcgtatt tcacgataca atcacgaaaa gcgaagataa agtgccattg cttggcgata   7200 

tacccgttat taaacgatta tttagcaaag aaagtgaacg acatcaaaaa cgtgagctag   7260 

tgattttcgt cacgccacat attttaaaag caggagaaaa cgttagaggc gttgaaacaa   7320 

aaaagtgagg gtaaaaaata actttttaaa tgatgaattt ttttaatttt cgctgtatcc   7380 

actgtcgtgg caatcttcat atcgcaaaaa atgggttatg ttcaggttgc caaaaacaaa   7440 

ttaaatcttt tccttattgc ggtcattgtg gttcggaatt gcaatattat gcgcagcatt   7500 

gtgggaattg tcttaaacaa gaaccaagtt gggataagat ggtcattatt gggcattata   7560 

ttgaacctct ttcgatattg attcagcgtt ttaaatttca aaatcaattt tggattgacc   7620 

gcactttagc tcggctttta tatcttgcgg tacgtgatgc taaacgaacg catcaactta   7680 

aattgccaga ggcaatcatt ccagtgcctt tatatcattt tcgtcagtgg cgacggggtt   7740 

ataatcaggc agatttatta tctcagcaat taagtcgttg gctggatatt cctaatttga   7800 

acaatatcgt aaagcgtgtg aaacacacct atactcaacg tggtttgagt gcaaaagatc   7860 

gtcgtcagaa tttaaaaaat gccttttctc ttgctgtttc gaaaaatgaa tttccttatc   7920 

gtcgtgttgc gttggtggat gatgtgatta ctactggttc tacactcaat gaaatctcaa   7980 

aattgttgcg aaaattaggt gtggaggaga ttcaagtgtg ggggctggca cgagcttaat   8040 

ataaagcact ggaaaaaaaa gcgcgataag cgtattattc ccgatacttt ctctcaagta   8100 

tttaggacat aattatggaa caagcaaccc agcaaatcgc tatttctgat gccgcacaag   8160 

cgcattttcg aaaactttta gacacccaag aagaaggaac gcatattcgt attttcgcgg   8220 

ttaatcctgg tacgcctaat gcggaatgtg gcgtatctta ttgccccccg aatgccgtgg   8280 

aagaaagcga tattgaaatg aaatataata ctttttctgc atttattgat gaagtgagtt   8340 

tgcctttctt agaagaagca gaaattgatt atgttaccga agagcttggt gcgcaactga   8400 

ccttaaaagc accgaatgcc aaaatgcgta aggtggctga tgatgcgcca ttgattgaac   8460 

gtgttgaata tgtaattcaa actcaaatta acccacagct tgcaaatcac ggtggacgta   8520 

taaccttaat tgaaattact gaagatggtt acgcagtttt acaatttggt ggtggctgta   8580 

acggttgttc aatggtggat gttacgttaa aagatggggt agaaaaacaa cttgttagct   8640 

tattcccgaa tgaattaaaa ggtgcaaaag atataactga gcatcaacgt ggcgaacatt   8700 

cttattatta gtgagttata aaagaagatt tataatgacc gcacttttga aagtgcggtt   8760 

atttttatgg agaaaaaatg aaaatacttc aacaagatga ttttggttat tggttgctta   8820 

cacaaggttc taatctgtat ttagtgaata atgaattgcc ttttggtatc gctaaagata   8880 

ttgatttgga aggattgcag gcaatgcaaa ttggggaatg gaaaaattat ccgttgtggc   8940 

ttgtggctga gcaagaaagt gatgaacgag aatatgtgag tttgagtaac ttgctttcac   9000 

tgccagagga tgaattccat atattaagcc gaggtgtgga aattaatcat tttctgaaaa   9060 

cccataaatt ctgtggaaag tgcggtcata aaacacaaca                         9100 

 
           
             28  
             525  
             DNA  
             Moraxella catarrhalis  
           
            28 

aaaaatcgac tgccgtcatt ttcaaccacc acatagctca tattcgcaag ccaatgtatt     60 

gaccgttggg aataataaca gccccaaaac aatgaaacat atggtgatga gccaaacata    120 

ctttcctgca gattttggaa tcatatcgcc atcagcacca gtatggtttg accagtattt    180 

aacgccatag acatgtgtaa aaaaattaaa taacggtgca agcatgagac caacggcacc    240 

tgatgtacct tgtacgatga cctcacctgc tgtggcaacc ataccaagtc cattgcctgt    300 

gatatttttg cgaaaagaca aacttaccac acagaccaag ccgatgattg agatgacaaa    360 

ataaaaccaa tccaaatgcg tgtgagctgt tgtggtccaa aatccagtaa atagtgcaat    420 

aaatccgcaa acaaaccaaa gtagcaccca gcttgttgtc caatcttttt taccaaagcc    480 

tgtgatgtta tctaaaatat caattttcat cagattttcc ctaat                    525 

 
           
             29  
             466  
             DNA  
             Moraxella catarrhalis  
           
            29 

taatgataac cagtcaagca agctcaaatc agggtcagcc tgttttgagc tttttatttt     60 

ttgatcatca tgcttaagat tcactctgcc atttttttac aacctgcacc acaagtcatc    120 

atcgcatttg caaaaatggt acaaacaagc cgtcagcgac ttaaacaaaa aaaggctcaa    180 

tctgcgtgtg tgcgttcact tttacaaatc accatgcacc gctttgacat tgttggtgaa    240 

tttcatgacc atgcacaccc ttattatatt aactcaaata aaatacgcta ctttgtcagc    300 

tttagccatt cagataatca agtcgctctc atcatcagct taacaccttg tgccattgac    360 

atagaagtta acgatattaa atacagtgtg gttgaacgat actttcatcc caatgaaatt    420 

tatctactta ctcaatttag ctctactgat aggcaacagc ttatta                   466 

 
           
             30  
             631  
             DNA  
             Streptococcus pneumoniae  
           
            30 

gatctttgat tttcattgag tattactctc tcttgtcact tctttctatt ttaccataaa     60 

gtccagcctt tgaagaactt ttactagaag acaaggggct tctgtctcta tttgccatct    120 

taggcatcaa aaaagagggg tcatccctct ttacgaattc aatgctacta gggtatccaa    180 

atactggttg ttgatgactg ccaaaatata ggtatctgct ttcaagaggt catctggtcc    240 

aaattcaaca tccaatgggg aattttcctg ctctcggaaa cccaaaatat tcagattgta    300 

tttgccacgg aggtctaatt tacttcagac tttgacctgc ccaagactga ggaattttca    360 

tctccacgat agacacattt ttatccaact gaaagacatc aacactatta tgaaaagaat    420 

ggtctgtgct agagactgcc ccatttcata ctctggcgag ataaccgagt cagctccaat    480 

cttttctagc actttcttag cggtctgact tttgacctta gcaataacag tcggtacccc    540 

caaactctta cagtgcataa ccgcaagcac actcgactcc agattttcac ctgtcgcgac    600 

tacaacggta tcgcaggtat caatccctgc t                                   631 

 
           
             31  
             3754  
             DNA  
             Streptococcus pneumoniae  
           
            31 

ccaatatttt ggtcagcata gtgttctttt tcagtggtaa cagcttgcaa tacttgagca     60 

gaaatggcag atttatcaag gaaaaagtta acgtaaggtc ctgttgcgac aactttttca    120 

aaggcttggc tgttcatttt ttcagccagt tcagccgcaa tcatttgtgg tgctttacgt    180 

tcgacttttg caagagaaaa agcagggaaa gcaatgtctc ccatttctga gtttttaggg    240 

gtttccagta actttaaaat agcctcttgg tccaggctat caatgatgct agataattcg    300 

ctagcaatca attcttttgt attcattaag agctcctttt tggacttttc tactatttta    360 

tcacaatttt aaagaaagaa gaaaaaattt ttgaaatctc ctgttttttt ggtataatat    420 

ggttataaat atagttataa atatagttat aaatatgcac gcaagaggat tttatgagaa    480 

aaagagatcg tcatcagtta ataaaaaaaa tgattactga ggagaaatta agtacacaaa    540 

aagaaattca agatcggttg gaggcgcaca atgtttgtgt gacgcagaca accttgtctc    600 

gtgatttgcg cgaaatcggc ttgaccaagg tcaagaaaaa tgatatggtg tattatgtac    660 

tagtaaatga gacagaaaag attgatttgg tggaattttt gtctcatcat ttagaaggtg    720 

ttgcaagagc agagtttacc ttggtgcttc ataccaaatt gggagaagcc tctgttttgg    780 

caaatattgt agatgtaaac aaggatgaat ggattttagg aacagttgct ggtgccaata    840 

ccttattggt tatttgtcga gatcagcacg ttgccaaact catggaagat cgtttgctag    900 

atttgatgaa agataagtaa ggtcttggga gttgctctca agacttattt ttgaaaagga    960 

gagacagaaa atggcgatag aaaagctatc acccggcatg caacagtatg tggatattaa   1020 

aaagcaatat ccagatgctt ttttgctctt tcggatgggt gatttttatg aattatttta   1080 

tgaggatgcg gtcaatgctg cgcagattct ggaaatttcc ttaacgagtc gcaacaagaa   1140 

tgccgacaat ccgatcccta tggcgggtgt tccctatcat tctgcccaac agtatatcga   1200 

tgtcttgatt gagcagggtt ataaggtggc tatcgcagag cagatggaag atcctaaaca   1260 

agcagttggg gttgttaaac gagaggttgt tcaggtcatt acgccaggga cagtggtcga   1320 

tagcagtaag ccggacagtc agaataattt tttggtttcc atagaccgcg aaggcaatca   1380 

atttggccta gcttatatgg atttggtgac gggtgacttt tatgtgacag gtcttttgga   1440 

tttcacgctg gtttgtgggg aaatccgtaa cctcaaggct cgagaagtgg tgttgggtta   1500 

tgacttgtct gaggaagaag aacaaatcct cagccgccag atgaatctgg tactctctta   1560 

tgaaaaagaa agctttgaag accttcattt attggatttg cgattggcaa cggtggagca   1620 

aacggcatct agtaagctgc tccagtatgt tcatcggact cagatgaggg aattgaacca   1680 

cctcaaacct gttatccgct acgaaattaa ggatttcttg cagatggatt atgcgaccaa   1740 

ggctagtctg gatttggttg agaatgctcg ctcaggtaag aaacaaggca gtcttttctg   1800 

gcttttggat gaaaccaaaa cggctatggg gatgcgtctc ttgcgttctt ggattcatcg   1860 

ccccttgatt gataaggaac gaatcgtcca acgtcaagaa gtagtgcagg tctttctcga   1920 

ccatttcttt gagcgtagtg acttgacaga cagtctcaag ggtgtttatg acattgagcg   1980 

cttggctagt cgtgtttctt ttggcaaaac caatccaaag gatctcttgc agttggcgac   2040 

taccttgtct agtgtgccac ggattcgtgc gattttagaa gggatggagc aacctactct   2100 

agcctatctc atcgcacaac tggatgcaat ccctgagttg gagagtttga ttagcgcagc   2160 

gattgctcct gaagctcctc atgtgattac agatggggga attatccgga ctggatttga   2220 

tgagacttta gacaagtatc gttgcgttct cagagaaggg actagctgga ttgctgagat   2280 

tgaggctaag gagcgagaaa actctggtat cagcacgctc aagattgact acaataaaaa   2340 

ggatggctac tattttcatg tgaccaattc gcaactggga aatgtgccag cccacttttt   2400 

ccgcaaggcg acgctgaaaa actcagaacg ctttggaacc gaagaattag cccgtatcga   2460 

gggagatatg cttgaggcgc gtgagaagtc agccaacctc gaatacgaaa tatttatgcg   2520 

cattcgtgaa gaggtcggca agtacatcca gcgtttacaa gctctagccc aaggaattgc   2580 

gacggttgat gtcttacaga gtctggcggt tgtggctgaa acccagcatt tgattcgacc   2640 

tgagtttggt gacgattcac aaattgatat ccggaaaggg cgccatgctg tcgttgaaaa   2700 

ggttatgggg gctcagacct atattccaaa tacgattcag atggcagaag ataccagtat   2760 

tcaattggtt acagggccaa acatgagtgg gaagtctacc tatatgcgtc agttagccat   2820 

gacggcggtt atggcccagc tgggttccta tgttcctgct gaaagcgccc atttaccgat   2880 

ttttgatgcg atttttaccc gtatcggagc agcagatgac ttggtttcgg gtcagtcaac   2940 

ctttatggtg gagatgatgg aggccaataa tgccatttcg catgcgacca agaactctct   3000 

cattctcttt gatgaattgg gacgtggaac tgcaacttat gacgggatgg ctcttgctca   3060 

gtccatcatc gaatatatcc atgagcacat cggagctaag accctctttg cgacccacta   3120 

ccatgagttg actagtctgg agtctagttt acaacacttg gtcaatgtcc acgtggcaac   3180 

tttggagcag gatgggcagg tcaccttcct tcacaagatt gaaccgggac cagctgataa   3240 

atcctacggt atccatgttg ccaagattgc tggcttgcca gcagaccttt tagcaagggc   3300 

ggataagatt ttgactcagc tagagaatca aggaacagag agtcctcctc ccatgagaca   3360 

aactagtgct gtcactgaac agatttcact ctttgatagg gcagaagagc atcctatcct   3420 

agcagaatta gctaaactgg atgtgtataa tatgacacct atgcaggtta tgaatgtctt   3480 

agtagagtta aaacagaaac tataaaacca agactcacta gttaatctag ctgtatcaag   3540 

gagacttctt tgacaattct ccactttttt gctagaataa catcacacaa acagaatgaa   3600 

aagggctgac gcattgtcgc tcccttttgt ctatttttta aggagaaagt atgctgattc   3660 

agaaaataaa aacctacaag tggcaggccc tgcttcgctc ctgatgacag gcttgatggt   3720 

tgctagttca cttctgcaac cgcgttatct gcag                               3754 

 
           
             32  
             1337  
             DNA  
             Streptococcus pyogenes  
           
            32 

aacaaaataa aagaacttac ctattttcca tccaaaatgt ttagcaatca tcatctgcaa     60 

ggcaacgtat tgcatggcat tgatgtgatg agcaactaat atgtcattag aacgttgcgt    120 

caaactagca tctaaataaa gatcgaaatg cagttatcaa aaatgcaagc tcctatcggc    180 

ccttgtttta attattactc acattgcctt aatgtattta cttgcttatt attaactttt    240 

ttgctaagtt agtagcgtca gttattcatt gaaaggacat tattatgaaa attcttgtaa    300 

caggctttga tccctttggc ggcgaagcta ttaatcctgc ccttgaagct atcaagaaat    360 

tgccagcaac cattcatgga gcagaaatca aatgtattga agttccaacg gtttttcaaa    420 

aatctgccga tgtgctccag cagcatatcg aaagctttca acctgatgca gtcctttgta    480 

ttgggcaagc tggtggccgg actggactaa cgccagaacg cgttgccatt aatcaagacg    540 

atgctcgcat tcctgataac gaagggaatc agcctattga tacacctatt cgtgcagatg    600 

gtaaagcagc ttatttttca accttgccaa tcaaagcgat ggttgctgcc attcatcagg    660 

ctgggcttcc tgcttctgtt tctaatacag ctggtacctt tgtttgcaat catttgatgt    720 

atcaagccct ttacttagtg gataaatatt gtccaaatgc caaagctggg tttatgcata    780 

ttccctttat gatggaacag gttgttgata aacctaatac agctgccatg aacctcgatg    840 

atattacaag aggaattgag gctgctattt ttgccattgt cgatttcaaa gatcgttccg    900 

atttaaaacg tgtagggggc gctactcact gactgtgacg ctactaaacc tattttaaaa    960 

aaacagagat atgaactaac tctgtttttt ttgtgctaaa aatgaaagac ctagggaaac   1020 

ttttcatcgg tctttctcaa ttgtcatctt aatctaatac tacttctaac atcagcgggt   1080 

atagtttgcc agtaattaag aaacgttgtt gatctaaatg agcaatccca ttcaaaacat   1140 

taaggtcagg gtaatgggac ttatcaagat ttaaggcttt taacaaagga ctaatatcat   1200 

aggtggctac cacctttcca gaatcaggtt ggagtttgac aatagtattg gtttgccaaa   1260 

tattggcata gagataacca tctacatact ctaattcgtt aagcattgag atagggacac   1320 

tttctatagc aactagt                                                  1337 

 
           
             33  
             1837  
             DNA  
             Streptococcus pyogenes  
           
            33 

tcatgtttga cagcttatca tcgataagct tacttttcga atcaggtcta tccttgaaac     60 

aggtgcaaca tagattaggg catggagatt taccagacaa ctatgaacgt atatactcac    120 

atcacgcaat cggcaattga tgacattgga actaaattca atcaatttgt tactaacaag    180 

caactagatt gacaactaat tctcaacaaa cgttaattta acaacattca agtaactccc    240 

accagctcca tcaatgctta ccgtaagtaa tcataactta ctaaaacctt gttacatcaa    300 

ggttttttct ttttgtcttg ttcatgagtt accataactt tctatattat tgacaactaa    360 

attgacaact cttcaattat ttttctgtct actcaaagtt ttcttcattt gatatagtct    420 

aattccacca tcacttcttc cactctctct accgtcacaa cttcatcatc tctcactttt    480 

tcgtgtggta acacataatc aaatatcttt ccgtttttac gcactatcgc tactgtgtca    540 

cctaaaatat accccttatc aatcgcttct ttaaactcat ctatatataa catatttcat    600 

cctcctacct atctattcgt aaaaagataa aaataactat tgtttttttt gttattttat    660 

aataaaatta ttaatataag ttaatgtttt ttaaaaatat acaattttat tctatttata    720 

gttagctatt ttttcattgt tagtaatatt ggtgaattgt aataaccttt ttaaatctag    780 

aggagaaccc agatataaaa tggaggaata ttaatggaaa acaataaaaa agtattgaag    840 

aaaatggtat tttttgtttt agtgacattt cttggactaa caatctcgca agaggtattt    900 

gctcaacaag accccgatcc aagccaactt cacagatcta gtttagttaa aaaccttcaa    960 

aatatatatt ttctttatga gggtgaccct gttactcacg agaatgtgaa atctgttgat   1020 

caacttttat ctcacgattt aatatataat gtttcagggc caaattatga taaattaaaa   1080 

actgaactta agaaccaaga gatggcaact ttatttaagg ataaaaacgt tgatatttat   1140 

ggtgtagaat attaccatct ctgttattta tgtgaaaatg cagaaaggag tgcatgtatc   1200 

tacggagggg taacaaatca tgaagggaat catttagaaa ttcctaaaaa gatagtcgtt   1260 

aaagtatcaa tcgatggtat ccaaagccta tcatttgata ttgaaacaaa taaaaaaatg   1320 

gtaactgctc aagaattaga ctataaagtt agaaaatatc ttacagataa taagcaacta   1380 

tatactaatg gaccttctaa atatgaaact ggatatataa agttcatacc taagaataaa   1440 

gaaagttttt ggtttgattt tttccctgaa ccagaattta ctcaatctaa atatcttatg   1500 

atatataaag ataatgaaac gcttgactca aacacaagcc aaattgaagt ctacctaaca   1560 

accaagtaac tttttgcttt tggcaacctt acctactgct ggatttagaa attttattgc   1620 

aattctttta ttaatgtaaa aaccgctcat ttgatgagcg gttttgtctt atctaaagga   1680 

gctttacctc ctaatgctgc aaaattttaa atgttggatt tttgtatttg tctattgtat   1740 

ttgatgggta atcccatttt tcgacagaca tcgtcgtgcc acctctaaca ccaaaatcat   1800 

agacaggagc ttgtagctta gcaactattt tatcgtc                            1837 

 
           
             34  
             841  
             DNA  
             Streptococcus pneumoniae  
           
            34 

gatcaatatg tccaagaaac cacatgttcc taagacaaga gctaacagac tggccgtcaa     60 

taatagtatt gttctttttt tcatcattac tccttaacta gtgtttaact gattaattag    120 

ccagtaaata gtttatcttt atttacacta tctgttaaga tatagtaaaa tgaaataaga    180 

acaggacagt caaatcgatt tctaacaatg ttttagaagt agaggtatac tattctaatt    240 

tcaatctact atattttgca cattttcata aaaaaaatga gaactagaac tcacattctg    300 

ctctcatttt tcgttttccc gttctcctat cctgttttta ggagttagaa aatgctgcta    360 

cctttactta ctctccttta ataaagccaa tagtttttca gcttctgcca taatagtatt    420 

gttgtcctgg gtgccaaata gtaaattatt ttttaatcct gtgagagtct ctttggcatt    480 

ggacttgata attggattct ggatttttcc aagtaaatct tcagcctctc tcagttttct    540 

taacctttca gtctcgacct gaggttcttc tgattcctct ggtgattctt ctggtgattc    600 

ttcttctggt tcctctgttg gttttggaga ctctggtttc tcgctttgcg gtttctcttc    660 

tcgaggggtt tcttcctcag gtttttctgt ctgaggtttc tcctcgtttg gtttttccgt    720 

ttgattggta tcagcttgac catttttgtt tctttgaaca tggtcgctag cgttaccaaa    780 

accattatct gaatgcgacg ttcgtttgga tgttcgacat agtacttgac agtcgccaaa    840 

a                                                                    841 

 
           
             35  
             4500  
             DNA  
             Streptococcus pneumoniae  
           
            35 

gatcaggaca gtcaaatcga tttctaacaa tgttttagaa gtagatgtgt actattctag     60 

tttcaatcta ttatatttat agaatttttt gttgctagat ttgtcaaatt gcttaaaata    120 

atttttttca gaaagcaaaa gccgatacct atcgagtagg gtagttcttg ctatcgtcag    180 

gcttgtctgt aggtgttaac acttttcaaa aatctcttca aacaacgtca gctttgcctt    240 

gccgtatata tgttactgac ttcgtcagtt ctatctgcca cctcaaaacg gtgttttgag    300 

ctgacttcgt cagttctatc cacaacctca aaacagtgtt ttgagctgac ttcgtcagtt    360 

ctatccacaa cctcaaaaca gtgttttgag ctgactttgt cagtcttatc tacaacctca    420 

aaacagtgtt ttgagcatca tgcggctagc ttcttagttt gctctttgat tttcattgag    480 

tataaaaaca gatgagtttc tgttttcttt ttatggacta taaatgttca gctgaaacta    540 

ctttcaagga cattattata taaaagaatt ttttgaaact aaaatctact atattacact    600 

atattgaaag cgttttaaaa atgaggtata ataaatttac taacacttat aaaaagtgat    660 

agaatctatc tttatgtata tttaaagata gattgctgta aaaatagtag tagctatgcg    720 

aaataacaga tagagagaag ggattgaagc ttagaaaagg ggaataatat gatatttaag    780 

gcattcaaga caaaaaagca gagaaaaaga caagttgaac tacttttgac agtttttttc    840 

gacagttttc tgattgattt atttcttcac ttatttggga ttgtcccctt taagctggat    900 

aagattctga ttgtgagctt gattatattt cccattattt ctacaagtat ttatgcttat    960 

gaaaagctat ttgaaaaagt gttcgataag gattgagcag gaagtatggt gtaaatagca   1020 

taagctgatg tccatcattt gcttataaag agatatttta gtttaattgc agcggtgtcc   1080 

tggtagataa actagattgg caggagtctg attggagaaa ggagagggga aatttggcac   1140 

caatttgaga tagtttgttt agttcatttt tgtcatttaa atgaactgta gtaaaagaaa   1200 

gttaataaaa gacaaactaa gtgcattttc tggaataaat gtcttatttc agaaatcggg   1260 

atatagatat agagaggaac agtatgaatc ggagtgttca agaacgtaag tgtcgttata   1320 

gcattaggaa actatcggta ggagcggttt ctatgattgt aggagcagtg gtatttggaa   1380 

cgtctcctgt tttagctcaa gaaggggcaa gtgagcaacc tctggcaaat gaaactcaac   1440 

tttcggggga gagctcaacc ctaactgata cagaaaagag ccagccttct tcagagactg   1500 

aactttctgg caataagcaa gaacaagaaa ggaaagataa gcaagaagaa aaaattccaa   1560 

gagattacta tgcacgagat ttggaaaatg tcgaaacagt gatagaaaaa gaagatgttg   1620 

aaaccaatgc ttcaaatggt cagagagttg atttatcaag tgaactagat aaactaaaga   1680 

aacttgaaaa cgcaacagtt cacatggagt ttaagccaga tgccaaggcc ccagcattct   1740 

ataatctctt ttctgtgtca agtgctacta aaaaagatga gtacttcact atggcagttt   1800 

acaataatac tgctactcta gaggggcgtg gttcggatgg gaaacagttt tacaataatt   1860 

acaacgatgc acccttaaaa gttaaaccag gtcagtggaa ttctgtgact ttcacagttg   1920 

aaaaaccgac agcagaacta cctaaaggcc gagtgcgcct ctacgtaaac ggggtattat   1980 

ctcgaacaag tctgagatct ggcaatttca ttaaagatat gccagatgta acgcatgtgc   2040 

aaatcggagc aaccaagcgt gccaacaata cggtttgggg gtcaaatcta cagattcgga   2100 

atctcactgt gtataatcgt gctttaacac cagaagaggt acaaaaacgt agtcaacttt   2160 

ttaaacgctc agatttagaa aaaaaactac ctgaaggagc ggctttaaca gagaaaacgg   2220 

acatattcga aagcgggcgt aacggtaaac caaataaaga tggaatcaag agttatcgta   2280 

ttccagcact tctcaagaca gataaaggaa ctttgatcgc aggtgcagat gaacgccgtc   2340 

tccattcgag tgactggggt gatatcggta tggtcatcag acgtagtgaa gataatggta   2400 

aaacttgggg tgaccgagta accattacca acttacgtga caatccaaaa gcttctgacc   2460 

catcgatcgg ttcaccagtg aatatcgata tggtgttggt tcaagatcct gaaaccaaac   2520 

gaatcttttc tatctatgac atgttcccag aagggaaggg aatctttgga atgtcttcac   2580 

aaaaagaaga agcctacaaa aaaatcgatg gaaaaaccta tcaaatcctc tatcgtgaag   2640 

gagaaaaggg agcttatacc attcgagaaa atggtactgt ctatacacca gatggtaagg   2700 

cgacagacta tcgcgttgtt gtagatcctg ttaaaccagc ctatagcgac aagggggatc   2760 

tatacaaggg taaccaatta ctaggcaata tctacttcac aacaaacaaa acttctccat   2820 

ttagaattgc caaggatagc tatctatgga tgtcctacag tgatgacgac gggaagacat   2880 

ggtcagcgcc tcaagatatt actccgatgg tcaaagccga ttggatgaaa ttcttgggtg   2940 

taggtcctgg aacaggaatt gtacttcgga atgggcctca caagggacgg attttgatac   3000 

cggtttatac gactaataat gtatctcact taaatggctc gcaatcttct cgtatcatct   3060 

attcagatga tcatggaaaa acttggcatg ctggagaagc ggtcaacgat aaccgtcagg   3120 

tagacggtca aaagatccac tcttctacga tgaacaatag acgtgcgcaa aatacagaat   3180 

caacggtggt acaactaaac aatggagatg ttaaactctt tatgcgtggt ttgactggag   3240 

atcttcaggt tgctacaagt aaagacggag gagtgacttg ggagaaggat atcaaacgtt   3300 

atccacaggt taaagatgtc tatgttcaaa tgtctgctat ccatacgatg cacgaaggaa   3360 

aagaatacat catcctcagt aatgcaggtg gaccgaaacg tgaaaatggg atggtccact   3420 

tggcacgtgt cgaagaaaat ggtgagttga cttggctcaa acacaatcca attcaaaaag   3480 

gagagtttgc ctataattcg ctccaagaat taggaaatgg ggagtatggc atcttgtatg   3540 

aacatactga aaaaggacaa aatgcctata ccctatcatt tagaaaattt aattgggact   3600 

ttttgagcaa agatctgatt tctcctaccg aagcgaaagt gaagcgaact agagagatgg   3660 

gcaaaggagt tattggcttg gagttcgact cagaagtatt ggtcaacaag gctccaaccc   3720 

ttcaattggc aaatggtaaa acagcacgct tcatgaccca gtatgataca aaaaccctcc   3780 

tatttacagt ggattcagag gatatgggtc aaaaagttac aggtttggca gaaggtgcaa   3840 

ttgaaagtat gcataattta ccagtctctg tggcgggcac taagctttcg aatggaatga   3900 

acggaagtga agctgctgtt catgaagtgc cagaatacac aggcccatta gggacatccg   3960 

gcgaagagcc agctccaaca gtcgagaagc cagaatacac aggcccacta gggacatccg   4020 

gcgaagagcc agccccgaca gtcgagaagc cagaatacac aggcccacta gggacagctg   4080 

gtgaagaagc agctccaaca gtcgagaagc cagaatttac agggggagtt aatggtacag   4140 

agccagctgt tcatgaaatc gcagagtata agggatctga ttcgcttgta actcttacta   4200 

caaaagaaga ttatacttac aaagctcctc ttgctcagca ggcacttcct gaaacaggaa   4260 

acaaggagag tgacctccta gcttcactag gactaacagc tttcttcctt ggtctgttta   4320 

cgctagggaa aaagagagaa caataagaga agaattctaa acatttgatt ttgtaaaaat   4380 

agaaggagat agcaggtttt caagcctgct atcttttttt gatgacattc aggctgatac   4440 

gaaatcataa gaggtctgaa actactttca gagtagtctg ttctataaaa tatagtagat   4500 

 
           
             36  
             705  
             DNA  
             Staphylococcus epidermidis  
           
            36 

gatccaagct tatcgatatc atcaaaaagt tggcgaacct tttcaaattt tggttcaaat     60 

tcttgagatg tatagaattc aaaatattta ccatttgcat agtctgattg ctcaaagtct    120 

tgatactttt ctccacgctc ttttgcaatt tccattgaac gttcgatgga ataatagttc    180 

ataatcataa agaatatatt agcaaagtct tttgcttctt cagattcata gccaatttta    240 

tttttagcta gataaccatg taagttcatt actcctagtc caacagaatg tagttcacta    300 

ttcgcttttt ttacacctgg tgcattttga atatttgctt catcacttac aactgtaaga    360 

gcatccatac ctgtgaacac agaatctctg aatttacctg attccataac attcactata    420 

ttcaatgagc ctaagttaca tgaaatatct cttttaattt catcttcaat tccatagtcg    480 

ttaattactg atgtctcttg taattggaaa atttcagtac ataaattact cattttaatt    540 

tgcccaatat ttgaattcgc atgtactttg tttgcattat ctttaaacat aagatatgga    600 

taaccagact gtaattgtgt ttgtgcaatc atatttaaca tttcacgtgc gtcttttttc    660 

tttttatcga tttcgaaccc ggggtaccga attcctcgag tctag                    705 

 
           
             37  
             442  
             DNA  
             Staphylococcus aureus  
           
            37 

gatcaatctt tgtcggtaca cgatattctt cacgactaaa taaacgctca ttcgcgattt     60 

tataaatgaa tgttgataac aatgttgtat tatctactga aatctcatta cgttgcatcg    120 

gaaacattgt gttctgtatg taaaagccgt cttgataatc tttagtagta ccgaagctgg    180 

tcatacgaga gttatatttt ccagccaaaa cgatattttt ataatcatta cgtgaaaaag    240 

gtttcccttc attatcacac aaatatttta gcttttcagt ttctatatca actgtagctt    300 

ctttatccat acgttgaata attgtacgat tctgacgcac catcttttgc acacctttaa    360 

tgttatttgt tttaaaagca tgaataagtt tttcaacaca acgatgtgaa tcttctaaga    420 

agtcaccgta aaatgaagga tc                                             442 

 
           
             38  
             20  
             DNA  
             Enterococcus faecalis  
           
            38 

gcaatacagg gaaaaatgtc                                                 20 

 
           
             39  
             20  
             DNA  
             Enterococcus faecalis  
           
            39 

cttcatcaaa caattaactc                                                 20 

 
           
             40  
             20  
             DNA  
             Enterococcus faecalis  
           
            40 

gaacagaaga agccaaaaaa                                                 20 

 
           
             41  
             20  
             DNA  
             Enterococcus faecalis  
           
            41 

gcaatcccaa ataatacggt                                                 20 

 
           
             42  
             19  
             DNA  
             Escherichia coli  
           
            42 

gctttccagc gtcatattg                                                  19 

 
           
             43  
             19  
             DNA  
             Escherichia coli  
           
            43 

gatctcgaca aaatggtga                                                  19 

 
           
             44  
             25  
             DNA  
             Escherichia coli  
           
            44 

cacccgcttg cgtggcaagc tgccc                                           25 

 
           
             45  
             25  
             DNA  
             Escherichia coli  
           
            45 

cgtttgtgga ttccagttcc atccg                                           25 

 
           
             46  
             17  
             DNA  
             Escherichia coli  
           
            46 

tcacccgctt gcgtggc                                                    17 

 
           
             47  
             19  
             DNA  
             Escherichia coli  
           
            47 

ggaactggaa tccacaaac                                                  19 

 
           
             48  
             25  
             DNA  
             Escherichia coli  
           
            48 

tgaagcactg gccgaaatgc tgcgt                                           25 

 
           
             49  
             25  
             DNA  
             Escherichia coli  
           
            49 

gatgtacagg attcgttgaa ggctt                                           25 

 
           
             50  
             25  
             DNA  
             Escherichia coli  
           
            50 

tagcgaaggc gtagcagaaa ctaac                                           25 

 
           
             51  
             25  
             DNA  
             Escherichia coli  
           
            51 

gcaacccgaa ctcaacgccg gattt                                           25 

 
           
             52  
             25  
             DNA  
             Escherichia coli  
           
            52 

atacacaagg gtcgcatctg cggcc                                           25 

 
           
             53  
             26  
             DNA  
             Escherichia coli  
           
            53 

tgcgtatgca ttgcagacct tgtggc                                          26 

 
           
             54  
             25  
             DNA  
             Escherichia coli  
           
            54 

gctttcactg gatatcgcgc ttggg                                           25 

 
           
             55  
             19  
             DNA  
             Escherichia coli  
           
            55 

gcaacccgaa ctcaacgcc                                                  19 

 
           
             56  
             19  
             DNA  
             Escherichia coli  
           
            56 

gcagatgcga cccttgtgt                                                  19 

 
           
             57  
             23  
             DNA  
             Klebsiella pneumoniae  
           
            57 

gtggtgtcgt tcagcgcttt cac                                             23 

 
           
             58  
             25  
             DNA  
             Klebsiella pneumoniae  
           
            58 

gcgatattca caccctacgc agcca                                           25 

 
           
             59  
             26  
             DNA  
             Klebsiella pneumoniae  
           
            59 

gtcgaaaatg ccggaagagg tatacg                                          26 

 
           
             60  
             26  
             DNA  
             Klebsiella pneumoniae  
           
            60 

actgagctgc agaccggtaa aactca                                          26 

 
           
             61  
             19  
             DNA  
             Klebsiella pneumoniae  
           
            61 

gacagtcagt tcgtcagcc                                                  19 

 
           
             62  
             19  
             DNA  
             Klebsiella pneumoniae  
           
            62 

cgtagggtgt gaatatcgc                                                  19 

 
           
             63  
             26  
             DNA  
             Klebsiella pneumoniae  
           
            63 

cgtgatggat attcttaacg aagggc                                          26 

 
           
             64  
             23  
             DNA  
             Klebsiella pneumoniae  
           
            64 

accaaactgt tgagccgcct gga                                             23 

 
           
             65  
             23  
             DNA  
             Klebsiella pneumoniae  
           
            65 

gtgatcgccc ctcatctgct act                                             23 

 
           
             66  
             26  
             DNA  
             Klebsiella pneumoniae  
           
            66 

cgcccttcgt taagaatatc catcac                                          26 

 
           
             67  
             19  
             DNA  
             Klebsiella pneumoniae  
           
            67 

tcgcccctca tctgctact                                                  19 

 
           
             68  
             19  
             DNA  
             Klebsiella pneumoniae  
           
            68 

gatcgtgatg gatattctt                                                  19 

 
           
             69  
             25  
             DNA  
             Klebsiella pneumoniae  
           
            69 

caggaagatg ctgcaccggt tgttg                                           25 

 
           
             70  
             25  
             DNA  
             Proteus mirabilis  
           
            70 

tggttcactg actttgcgat gtttc                                           25 

 
           
             71  
             25  
             DNA  
             Proteus mirabilis  
           
            71 

tcgaggatgg catgcactag aaaat                                           25 

 
           
             72  
             30  
             DNA  
             Proteus mirabilis  
           
            72 

cgctgattag gtttcgctaa aatcttatta                                      30 

 
           
             73  
             30  
             DNA  
             Proteus mirabilis  
           
            73 

ttgatcctca ttttattaat cacatgacca                                      30 

 
           
             74  
             19  
             DNA  
             Proteus mirabilis  
           
            74 

gaaacatcgc aaagtcagt                                                  19 

 
           
             75  
             20  
             DNA  
             Proteus mirabilis  
           
            75 

ataaaatgag gatcaagttc                                                 20 

 
           
             76  
             30  
             DNA  
             Proteus mirabilis  
           
            76 

ccgcctttag cattaattgg tgtttatagt                                      30 

 
           
             77  
             30  
             DNA  
             Proteus mirabilis  
           
            77 

cctattgcag ataccttaaa tgtcttgggc                                      30 

 
           
             78  
             26  
             DNA  
             Streptococcus pneumoniae  
           
            78 

agtaaaatga aataagaaca ggacag                                          26 

 
           
             79  
             25  
             DNA  
             Streptococcus pneumoniae  
           
            79 

aaaacaggat aggagaacgg gaaaa                                           25 

 
           
             80  
             25  
             DNA  
             Proteus mirabilis  
           
            80 

ttgagtgatg atttcactga ctccc                                           25 

 
           
             81  
             25  
             DNA  
             Proteus mirabilis  
           
            81 

gtcagacagt gatgctgacg acaca                                           25 

 
           
             82  
             27  
             DNA  
             Proteus mirabilis  
           
            82 

tggttgtcat gctgtttgtg tgaaaat                                         27 

 
           
             83  
             19  
             DNA  
             Pseudomonas aeruginosa  
           
            83 

cgagcgggtg gtgttcatc                                                  19 

 
           
             84  
             19  
             DNA  
             Pseudomonas aeruginosa  
           
            84 

caagtcgtcg tcggaggga                                                  19 

 
           
             85  
             19  
             DNA  
             Pseudomonas aeruginosa  
           
            85 

tcgctgttca tcaagaccc                                                  19 

 
           
             86  
             19  
             DNA  
             Pseudomonas aeruginosa  
           
            86 

ccgagaacca gacttcatc                                                  19 

 
           
             87  
             25  
             DNA  
             Pseudomonas aeruginosa  
           
            87 

aatgcggctg tacctcggcg ctggt                                           25 

 
           
             88  
             25  
             DNA  
             Pseudomonas aeruginosa  
           
            88 

ggcggagggc cagttgcacc tgcca                                           25 

 
           
             89  
             25  
             DNA  
             Pseudomonas aeruginosa  
           
            89 

agccctgctc ctcggcagcc tctgc                                           25 

 
           
             90  
             25  
             DNA  
             Pseudomonas aeruginosa  
           
            90 

tggcttttgc aaccgcgttc aggtt                                           25 

 
           
             91  
             25  
             DNA  
             Pseudomonas aeruginosa  
           
            91 

gcgcccgcga gggcatgctt cgatg                                           25 

 
           
             92  
             25  
             DNA  
             Pseudomonas aeruginosa  
           
            92 

acctgggcgc caactacaag ttcta                                           25 

 
           
             93  
             25  
             DNA  
             Pseudomonas aeruginosa  
           
            93 

ggctacgctg ccgggctgca ggccg                                           25 

 
           
             94  
             25  
             DNA  
             Pseudomonas aeruginosa  
           
            94 

ccgatctaca ccatcgagat gggcg                                           25 

 
           
             95  
             25  
             DNA  
             Pseudomonas aeruginosa  
           
            95 

gagcgcggct atgtgttcgt cggct                                           25 

 
           
             96  
             29  
             DNA  
             Staphylococcus saprophyticus  
           
            96 

cgtttttacc cttacctttt cgtactacc                                       29 

 
           
             97  
             30  
             DNA  
             Staphylococcus saprophyticus  
           
            97 

tcaggcagag gtagtacgaa aaggtaaggg                                      30 

 
           
             98  
             26  
             DNA  
             Staphylococcus saprophyticus  
           
            98 

cgtttttacc cttacctttt cgtact                                          26 

 
           
             99  
             28  
             DNA  
             Staphylococcus saprophyticus  
           
            99 

atcgatcatc acattccatt tgttttta                                        28 

 
           
             100  
             27  
             DNA  
             Staphylococcus saprophyticus  
           
            100 

caccaagttt gacacgtgaa gattcat                                         27 

 
           
             101  
             30  
             DNA  
             Staphylococcus saprophyticus  
           
            101 

atgagtgaag cggagtcaga ttatgtgcag                                      30 

 
           
             102  
             25  
             DNA  
             Staphylococcus saprophyticus  
           
            102 

cgctcattac gtacagtgac aatcg                                           25 

 
           
             103  
             30  
             DNA  
             Staphylococcus saprophyticus  
           
            103 

ctggttagct tgactcttaa caatcttgtc                                      30 

 
           
             104  
             30  
             DNA  
             Staphylococcus saprophyticus  
           
            104 

gacgcgattg tcactgtacg taatgagcga                                      30 

 
           
             105  
             28  
             DNA  
             Haemophilus influenzae  
           
            105 

gcgtcagaaa aagtaggcga aatgaaag                                        28 

 
           
             106  
             25  
             DNA  
             Haemophilus influenzae  
           
            106 

agcggctcta tcttgtaatg acaca                                           25 

 
           
             107  
             25  
             DNA  
             Haemophilus influenzae  
           
            107 

gaaacgtgaa ctcccctcta tataa                                           25 

 
           
             108  
             25  
             DNA  
             Moraxella catarrhalis  
           
            108 

gccccaaaac aatgaaacat atggt                                           25 

 
           
             109  
             25  
             DNA  
             Moraxella catarrhalis  
           
            109 

ctgcagattt tggaatcata tcgcc                                           25 

 
           
             110  
             25  
             DNA  
             Moraxella catarrhalis  
           
            110 

tggtttgacc agtatttaac gccat                                           25 

 
           
             111  
             25  
             DNA  
             Moraxella catarrhalis  
           
            111 

caacggcacc tgatgtacct tgtac                                           25 

 
           
             112  
             18  
             DNA  
             Moraxella catarrhalis  
           
            112 

ggcacctgat gtaccttg                                                   18 

 
           
             113  
             17  
             DNA  
             Moraxella catarrhalis  
           
            113 

aacagctcac acgcatt                                                    17 

 
           
             114  
             25  
             DNA  
             Moraxella catarrhalis  
           
            114 

ttacaacctg caccacaagt catca                                           25 

 
           
             115  
             25  
             DNA  
             Moraxella catarrhalis  
           
            115 

gtacaaacaa gccgtcagcg actta                                           25 

 
           
             116  
             23  
             DNA  
             Moraxella catarrhalis  
           
            116 

caatctgcgt gtgtgcgttc act                                             23 

 
           
             117  
             26  
             DNA  
             Moraxella catarrhalis  
           
            117 

gctactttgt cagctttagc cattca                                          26 

 
           
             118  
             24  
             DNA  
             Moraxella catarrhalis  
           
            118 

tgttttgagc tttttatttt ttga                                            24 

 
           
             119  
             22  
             DNA  
             Moraxella catarrhalis  
           
            119 

cgctgacggc ttgtttgtac ca                                              22 

 
           
             120  
             25  
             DNA  
             Streptococcus pneumoniae  
           
            120 

tctgtgctag agactgcccc atttc                                           25 

 
           
             121  
             25  
             DNA  
             Streptococcus pneumoniae  
           
            121 

cgatgtcttg attgagcagg gttat                                           25 

 
           
             122  
             25  
             DNA  
             Artificial Sequence  
             
               Description of Artificial Sequence 
      Oligonucleotide  
             
           
            122 

atcccacctt aggcggctgg ctcca                                           25 

 
           
             123  
             31  
             DNA  
             Artificial Sequence  
             
               Description of Artificial Sequence 
      Oligonucleotide  
             
           
            123 

acgtcaagtc atcatggccc ttacgagtag g                                    31 

 
           
             124  
             25  
             DNA  
             Artificial Sequence  
             
               Description of Artificial Sequence 
      Oligonucleotide  
             
           
            124 

gtgtgacggg cggtgtgtac aaggc                                           25 

 
           
             125  
             28  
             DNA  
             Artificial Sequence  
             
               Description of Artificial Sequence 
      Oligonucleotide  
             
           
            125 

gagttgcaga ctccaatccg gactacga                                        28 

 
           
             126  
             20  
             DNA  
             Artificial Sequence  
             
               Description of Artificial Sequence 
      Oligonucleotide  
             
           
            126 

ggaggaaggt ggggatgacg                                                 20 

 
           
             127  
             20  
             DNA  
             Artificial Sequence  
             
               Description of Artificial Sequence 
      Oligonucleotide  
             
           
            127 

atggtgtgac gggcggtgtg                                                 20 

 
           
             128  
             32  
             DNA  
             Artificial Sequence  
             
               Description of Artificial Sequence 
      Oligonucleotide  
             
           
            128 

ccctatacat caccttgcgg tttagcagag ag                                   32 

 
           
             129  
             28  
             DNA  
             Artificial Sequence  
             
               Description of Artificial Sequence 
      Oligonucleotide  
             
           
            129 

ggggggacca tcctccaagg ctaaatac                                        28 

 
           
             130  
             32  
             DNA  
             Artificial Sequence  
             
               Description of Artificial Sequence 
      Oligonucleotide  
             
           
            130 

cgtccacttt cgtgtttgca gagtgctgtg tt                                   32 

 
           
             131  
             20  
             DNA  
             Escherichia coli  
           
            131 

caggagtacg gtgattttta                                                 20 

 
           
             132  
             20  
             DNA  
             Escherichia coli  
           
            132 

atttctggtt tggtcataca                                                 20 

 
           
             133  
             20  
             DNA  
             Proteus mirabilis  
           
            133 

cgggagtcag tgaaatcatc                                                 20 

 
           
             134  
             20  
             DNA  
             Proteus mirabilis  
           
            134 

ctaaaatcgc cacacctctt                                                 20 

 
           
             135  
             18  
             DNA  
             Klebsiella pneumoniae  
           
            135 

gcagcgtggt gtcgttca                                                   18 

 
           
             136  
             18  
             DNA  
             Klebsiella pneumoniae  
           
            136 

agctggcaac ggctggtc                                                   18 

 
           
             137  
             20  
             DNA  
             Klebsiella pneumoniae  
           
            137 

attcacaccc tacgcagcca                                                 20 

 
           
             138  
             20  
             DNA  
             Klebsiella pneumoniae  
           
            138 

atccggcagc atctctttgt                                                 20 

 
           
             139  
             25  
             DNA  
             Staphylococcus saprophyticus  
           
            139 

ctggttagct tgactcttaa caatc                                           25 

 
           
             140  
             25  
             DNA  
             Staphylococcus saprophyticus  
           
            140 

tcttaacgat agaatggagc aactg                                           25 

 
           
             141  
             20  
             DNA  
             Streptococcus pyogenes  
           
            141 

tgaaaattct tgtaacaggc                                                 20 

 
           
             142  
             20  
             DNA  
             Streptococcus pyogenes  
           
            142 

ggccaccagc ttgcccaata                                                 20 

 
           
             143  
             20  
             DNA  
             Streptococcus pyogenes  
           
            143 

atattttctt tatgagggtg                                                 20 

 
           
             144  
             20  
             DNA  
             Streptococcus pyogenes  
           
            144 

atccttaaat aaagttgcca                                                 20 

 
           
             145  
             25  
             DNA  
             Staphylococcus epidermidis  
           
            145 

atcaaaaagt tggcgaacct tttca                                           25 

 
           
             146  
             25  
             DNA  
             Staphylococcus epidermidis  
           
            146 

caaaagagcg tggagaaaag tatca                                           25 

 
           
             147  
             30  
             DNA  
             Staphylococcus epidermidis  
           
            147 

tctcttttaa tttcatcttc aattccatag                                      30 

 
           
             148  
             30  
             DNA  
             Staphylococcus epidermidis  
           
            148 

aaacacaatt acagtctggt tatccatatc                                      30 

 
           
             149  
             30  
             DNA  
             Staphylococcus aureus  
           
            149 

cttcatttta cggtgacttc ttagaagatt                                      30 

 
           
             150  
             30  
             DNA  
             Staphylococcus aureus  
           
            150 

tcaactgtag cttctttatc catacgttga                                      30 

 
           
             151  
             30  
             DNA  
             Staphylococcus aureus  
           
            151 

atattttagc ttttcagttt ctatatcaac                                      30 

 
           
             152  
             30  
             DNA  
             Staphylococcus aureus  
           
            152 

aatctttgtc ggtacacgat attcttcacg                                      30 

 
           
             153  
             30  
             DNA  
             Staphylococcus aureus  
           
            153 

cgtaatgaga tttcagtaga taatacaaca                                      30 

 
           
             154  
             25  
             DNA  
             Haemophilus influenzae  
           
            154 

tttaacgatc cttttactcc ttttg                                           25 

 
           
             155  
             25  
             DNA  
             Haemophilus influenzae  
           
            155 

actgctgttg taaagaggtt aaaat                                           25 

 
           
             156  
             20  
             DNA  
             Streptococcus pneumoniae  
           
            156 

atttggtgac gggtgacttt                                                 20 

 
           
             157  
             20  
             DNA  
             Streptococcus pneumoniae  
           
            157 

gctgaggatt tgttcttctt                                                 20 

 
           
             158  
             20  
             DNA  
             Streptococcus pneumoniae  
           
            158 

gagcggtttc tatgattgta                                                 20 

 
           
             159  
             20  
             DNA  
             Streptococcus pneumoniae  
           
            159 

atctttcctt tcttgttctt                                                 20 

 
           
             160  
             18  
             DNA  
             Moraxella catarrhalis  
           
            160 

gctcaaatca gggtcagc                                                   18 

 
           
             161  
             861  
             DNA  
             Escherichia coli  
           
            161 

atgagtattc aacatttccg tgtcgccctt attccctttt ttgcggcatt ttgccttcct     60 

gtttttgctc acccagaaac gctggtgaaa gtaaaagatg ctgaagatca gttgggtgca    120 

cgagtgggtt acatcgaact ggatctcaac agcggtaaga tccttgagag ttttcgcccc    180 

gaagaacgtt ttccaatgat gagcactttt aaagttctgc tatgtggcgc ggtattatcc    240 

cgtgttgacg ccgggcaaga gcaactcggt cgccgcatac actattctca gaatgacttg    300 

gttgagtact caccagtcac agaaaagcat cttacggatg gcatgacagt aagagaatta    360 

tgcagtgctg ccataaccat gagtgataac actgcggcca acttacttct gacaacgatc    420 

ggaggaccga aggagctaac cgcttttttg cacaacatgg gggatcatgt aactcgcctt    480 

gatcgttggg aaccggagct gaatgaagcc ataccaaacg acgagcgtga caccacgatg    540 

cctgcagcaa tggcaacaac gttgcgcaaa ctattaactg gcgaactact tactctagct    600 

tcccggcaac aattaataga ctggatggag gcggataaag ttgcaggacc acttctgcgc    660 

tcggcccttc cggctggctg gtttattgct gataaatctg gagccggtga gcgtgggtct    720 

cgcggtatca ttgcagcact ggggccagat ggtaagccct cccgtatcgt agttatctac    780 

acgacgggga gtcaggcaac tatggatgaa cgaaatagac agatcgctga gataggtgcc    840 

tcactgatta agcattggta a                                              861 

 
           
             162  
             918  
             DNA  
             Pasteurella haemolytica  
           
            162 

atgttaaata agttaaaaat cggcacatta ttattgctga cattaacggc ttgttcgccc     60 

aattctgttc attcggtaac gtctaatccg cagcctgcta gtgcgcctgt gcaacaatca    120 

gccacacaag ccacctttca acagactttg gcgaatttgg aacagcagta tcaagcccga    180 

attggcgttt atgtatggga tacagaaacg ggacattctt tgtcttatcg tgcagatgaa    240 

cgctttgctt atgcgtccac tttcaaggcg ttgttggctg gggcggtgtt gcaatcgctg    300 

cctgaaaaag atttaaatcg taccatttca tatagccaaa aagatttggt tagttattct    360 

cccgaaaccc aaaaatacgt tggcaaaggc atgacgattg cccaattatg tgaagcagcc    420 

gtgcggttta gcgacaacag cgcgaccaat ttgctgctca aagaattggg tggcgtggaa    480 

caatatcaac gtattttgcg acaattaggc gataacgtaa cccataccaa tcggctagaa    540 

cccgatttaa atcaagccaa acccaacgat attcgtgata cgagtacacc caaacaaatg    600 

gcgatgaatt taaatgcgta tttattgggc aacacattaa ccgaatcgca aaaaacgatt    660 

ttgtggaatt ggttggacaa taacgcaaca ggcaatccat tgattcgcgc tgctacgcca    720 

acatcgtgga aagtgtacga taaaagcggg gcgggtaaat atggtgtacg caatgatatt    780 

gcggtggttc gcataccaaa tcgcaaaccg attgtgatgg caatcatgag tacgcaattt    840 

accgaagaag ccaaattcaa caataaatta gtagaagatg cagcaaagca agtatttcat    900 

actttacagc tcaactaa                                                  918 

 
           
             163  
             864  
             DNA  
             Klebsiella pneumoniae  
           
            163 

atgcgttata ttcgcctgtg tattatctcc ctgttagcca ccctgccgct ggcggtacac     60 

gccagcccgc agccgcttga gcaaattaaa ctaagcgaaa gccagctgtc gggccgcgta    120 

ggcatgatag aaatggatct ggccagcggc cgcacgctga ccgcctggcg cgccgatgaa    180 

cgctttccca tgatgagcac ctttaaagta gtgctctgcg gcgcagtgct ggcgcgggtg    240 

gatgccggtg acgaacagct ggagcgaaag atccactatc gccagcagga tctggtggac    300 

tactcgccgg tcagcgaaaa acaccttgcc gacgcaatga cggtcggcga actctgcgcc    360 

gccgccatta ccatgagcga taacagcgcc gccaatctgc tactggccac cgtcggcggc    420 

cccgcaggat tgactgcctt tttgcgccag atcggcgaca acgtcacccg ccttgaccgc    480 

tgggaaacgg aactgaatga ggcgcttccc ggcgacgccc gcgacaccac taccccggcc    540 

agcatggccg cgaccctgcg caacgttggc ctgaccagcc agcgtctgag cgcccgttcg    600 

caacggcagc tgctgcagtg gatggtggac gatcgggtcg ccggaccgtt gatccgctcc    660 

gtgctgccgg cgggctggtt tatcgccgat aagaccggag ctggcgagcg gggtgcgcgc    720 

gggattgtcg ccctgcttgg cccgaataac aaagcagagc gcattgtggt gatttatctg    780 

cgggataccc cggcgagcat ggccgagcga aatcagcaaa tcgccgggat cggcaaggcg    840 

ctgtacgagc actggcaacg ctaa                                           864 

 
           
             164  
             534  
             DNA  
             Klebsiella pneumoniae  
           
            164 

atggacacaa cgcaggtcac attgatacac aaaattctag ctgcggcaga tgagcgaaat     60 

ctgccgctct ggatcggtgg gggctgggcg atcgatgcac ggctagggcg tgtaacacgc    120 

aagcacgatg atattgatct gacgtttccc ggcgagaggc gcggcgagct cgaggcaata    180 

gttgaaatgc tcggcgggcg cgtcatggag gagttggact atggattctt agcggagatc    240 

ggggatgagt tacttgactg cgaacctgct tggtgggcag acgaagcgta tgaaatcgcg    300 

gaggctccgc agggctcgtg cccagaggcg gctgagggcg tcatcgccgg gcggccagtc    360 

cgttgtaaca gctgggaggc gatcatctgg gattactttt actatgccga tgaagtacca    420 

ccagtggact ggcctacaaa gcacatagag tcctacaggc tcgcatgcac ctcactcggg    480 

gcggaaaagg ttgaggtctt gcgtgccgct ttcaggtcgc gatatgcggc ctaa          534 

 
           
             165  
             465  
             DNA  
             Unknown Organism  
             
               Description of Unknown Organism 
      Enterobacteriaceae  
             
           
            165 

atgggcatca ttcgcacatg taggctcggc cctgaccaag tcaaatccat gcgggctgct     60 

cttgatcttt tcggtcgtga gttcggagac gtagccacct actcccaaca tcagccggac    120 

tccgattacc tcgggaactt gctccgtagt aagacattca tcgcgcttgc tgccttcgac    180 

caagaagcgg ttgttggcgc tctcgcggct tacgttctgc ccaggtttga gcagccgcgt    240 

agtgagatct atatctatga tctcgcagtc tccggcgagc accggaggca gggcattgcc    300 

accgcgctca tcaatctcct caagcatgag gccaacgcgc ttggtgctta tgtgatctac    360 

gtgcaagcag attacggtga cgatcccgca gtggctctct atacaaagtt gggcatacgg    420 

gaagaagtga tgcactttga tatcgaccca agtaccgcca cctaa                    465 

 
           
             166  
             861  
             DNA  
             Escherichia coli  
           
            166 

atgcatacgc ggaaggcaat aacggaggcg cttcaaaaac tcggagtcca aaccggtgac     60 

ctattgatgg tgcatgcctc acttaaagcg attggtccgg tcgaaggagg agcggagacg    120 

gtcgttgccg cgttacgctc cgcggttggg ccgactggca ctgtgatggg atacgcatcg    180 

tgggaccgat caccctacga ggagactcgt aatggcgctc ggttggatga caaaacccgc    240 

cgtacctggc cgccgttcga tcccgcaacg gccgggactt accgtgggtt cggcctgctg    300 

aatcagtttc tggttcaagc ccccggcgcg cggcgcagcg cgcaccccga tgcatcgatg    360 

gtcgcggttg gtccactggc tgaaacgctg acggagcctc acaagctcgg tcacgccttg    420 

ggggaagggt cgcccgtcga gcggttcgtt cgccttggcg ggaaggccct gctgttgggt    480 

gcgccgctaa actccgttac cgcattgcac tacgccgagg cggttgccga tatccccaac    540 

aaacggcggg tgacgtatga gatgccgatg cttggaagca acggcgaagt cgcctggaaa    600 

acggcatcgg attacgattc aaacggcatt ctcgattgct ttgctatcga aggaaagccg    660 

gatgcggtcg aaactatagc aaatgcttac gtgaagctcg gtcgccatcg agaaggtgtc    720 

gtgggctttg ctcagtgcta cctgttcgac gcgcaggaca tcgtgacgtt cggcgtcacc    780 

tatcttgaga agcatttcgg aaccactccg atcgtgccag cacacgaagt cgccgagtgc    840 

tcttgcgagc cttcaggtta g                                              861 

 
           
             167  
             816  
             DNA  
             Pseudomonas aeruginosa  
           
            167 

atgaccgatt tgaatatccc gcatacacac gcgcaccttg tagacgcatt tcaggcgctc     60 

ggcatccgcg cggggcaggc gctcatgctg cacgcatccg ttaaagcagt gggcgcggtg    120 

atgggcggcc ccaatgtgat cttgcaggcg ctcatggatg cgctcacgcc cgacggcacg    180 

ctgatgatgt atgcgggatg gcaagacatc cccgacttta tcgactcgct gccggacgcg    240 

ctcaaggccg tgtatcttga gcagcaccca ccctttgacc ccgccaccgc ccgcgccgtg    300 

cgcgaaaaca gcgtgctagc ggaatttttg cgcacatggc cgtgcgtgca tcgcagcgca    360 

aaccccgaag cctctatggt ggcggtaggc aggcaggccg ctttgctgac cgctaatcac    420 

gcgctggatt atggctacgg agtcgagtcg ccgctggcta aactggtggc aatagaagga    480 

tacgtgctga tgcttggcgc gccgctggat accatcacac tgctgcacca cgcggaatat    540 

ctggccaaga tgcgccacaa gaacgtggtc cgctacccgt gcccgattct gcgggacggg    600 

cgcaaagtgt gggtgaccgt tgaggactat gacaccggtg atccgcacga cgattatagt    660 

tttgagcaaa tcgcgcgcga ttatgtggcg cagggcggcg gcacacgcgg caaagtcggt    720 

gatgcggatg cttacctgtt cgccgcgcag gacctcacac ggtttgcggt gcagtggctt    780 

gaatcacggt tcggtgactc agcgtcatac ggatag                              816 

 
           
             168  
             498  
             DNA  
             Pseudomonas aeruginosa  
           
            168 

atgctctatg agtggctaaa tcgatctcat atcgtcgagt ggtggggcgg agaagaagca     60 

cgcccgacac ttgctgacgt acaggaacag tacttgccaa gcgttttagc gcaagagtcc    120 

gtcactccat acattgcaat gctgaatgga gagccgattg ggtatgccca gtcgtacgtt    180 

gctcttggaa gcggggacgg atggtgggaa gaagaaaccg atccaggagt acgcggaata    240 

gaccagttac tggcgaatgc atcacaactg ggcaaaggct tgggaaccaa gctggttcga    300 

gctctggttg agttgctgtt caatgatccc gaggtcacca agatccaaac ggacccgtcg    360 

ccgagcaact tgcgagcgat ccgatgctac gagaaagcgg ggtttgagag gcaaggtacc    420 

gtaaccaccc cagatggtcc agccgtgtac atggttcaaa cacgccaggc attcgagcga    480 

acacgcagtg atgcctaa                                                  498 

 
           
             169  
             2007  
             DNA  
             Staphylococcus aureus  
           
            169 

atgaaaaaga taaaaattgt tccacttatt ttaatagttg tagttgtcgg gtttggtata     60 

tatttttatg cttcaaaaga taaagaaatt aataatacta ttgatgcaat tgaagataaa    120 

aatttcaaac aagtttataa agatagcagt tatatttcta aaagcgataa tggtgaagta    180 

gaaatgactg aacgtccgat aaaaatatat aatagtttag gcgttaaaga tataaacatt    240 

caggatcgta aaataaaaaa agtatctaaa aataaaaaac gagtagatgc tcaatataaa    300 

attaaaacaa actacggtaa cattgatcgc aacgttcaat ttaattttgt taaagaagat    360 

ggtatgtgga agttagattg ggatcatagc gtcattattc caggaatgca gaaagaccaa    420 

agcatacata ttgaaaattt aaaatcagaa cgtggtaaaa ttttagaccg aaacaatgtg    480 

gaattggcca atacaggaac acatatgaga ttaggcatcg ttccaaagaa tgtatctaaa    540 

aaagattata aagcaatcgc taaagaacta agtatttctg aagactatat caacaacaaa    600 

tggatcaaaa ttgggtacaa gatgatacct tcgttccact ttaaaaccgt taaaaaaatg    660 

gatgaatatt taagtgattt cgcaaaaaaa tttcatctta caactaatga aacagaaagt    720 

cgtaactatc ctctagaaaa agcgacttca catctattag gttatgttgg tcccattaac    780 

tctgaagaat taaaacaaaa agaatataaa ggctataaag atgatgcagt tattggtaaa    840 

aagggactcg aaaaacttta cgataaaaag ctccaacatg aagatggcta tcgtgtcaca    900 

atcgttgacg ataatagcaa tacaatcgca catacattaa tagagaaaaa gaaaaaagat    960 

ggcaaagata ttcaactaac tattgatgct aaagttcaaa agagtattta taacaacatg   1020 

aaaaatgatt atggctcagg tactgctatc caccctcaaa caggtgaatt attagcactt   1080 

gtaagcacac cttcatatga cgtctatcca tttatgtatg gcatgagtaa cgaagaatat   1140 

aataaattaa ccgaagataa aaaagaacct ctgctcaaca agttccagat tacaacttca   1200 

ccaggttcaa ctcaaaaaat attaacagca atgattgggt taaataacaa aacattagac   1260 

gataaaacaa gttataaaat cgatggtaaa ggttggcaaa aagataaatc ttggggtggt   1320 

tacaacgtta caagatatga agtggtaaat ggtaatatcg acttaaaaca agcaatagaa   1380 

tcatcagata acattttctt tgctagagta gcactcgaat taggcagtaa gaaatttgaa   1440 

aaaggcatga aaaaactagg tgttggtgaa gatataccaa gtgattatcc attttataat   1500 

gctcaaattt caaacaaaaa tttagataat gaaatattat tagctgattc aggttacgga   1560 

caaggtgaaa tactgattaa cccagtacag atcctttcaa tctatagcgc attagaaaat   1620 

aatggcaata ttaacgcacc tcacttatta aaagacacga aaaacaaagt ttggaagaaa   1680 

aatattattt ccaaagaaaa tatcaatcta ttaaatgatg gtatgcaaca agtcgtaaat   1740 

aaaacacata aagaagatat ttatagatct tatgcaaact taattggcaa atccggtact   1800 

gcagaactca aaatgaaaca aggagaaagt ggcagacaaa ttgggtggtt tatatcatat   1860 

gataaagata atccaaacat gatgatggct attaatgtta aagatgtaca agataaagga   1920 

atggctagct acaatgccaa aatctcaggt aaagtgtatg atgagctata tgagaacggt   1980 

aataaaaaat acgatataga tgaataa                                       2007 

 
           
             170  
             2607  
             DNA  
             Enterococcus faecium  
           
            170 

atgaataaca tcggcattac tgtttatgga tgtgagcagg atgaggcaga tgcattccat     60 

gctctttcgc ctcgctttgg cgttatggca acgataatta acgccaacgt gtcggaatcc    120 

aacgccaaat ccgcgccttt caatcaatgt atcagtgtgg gacataaatc agagatttcc    180 

gcctctattc ttcttgcgct gaagagagcc ggtgtgaaat atatttctac ccgaagcatc    240 

ggctgcaatc atatagatac aactgctgct aagagaatgg gcatcactgt cgacaatgtg    300 

gcgtactcgc cggatagcgt tgccgattat actatgatgc taattcttat ggcagtacgc    360 

aacgtaaaat cgattgtgcg ctctgtggaa aaacatgatt tcaggttgga cagcgaccgt    420 

ggcaaggtac tcagcgacat gacagttggt gtggtgggaa cgggccagat aggcaaagcg    480 

gttattgagc ggctgcgagg atttggatgt aaagtgttgg cttatagtcg cagccgaagt    540 

atagaggtaa actatgtacc gtttgatgag ttgctgcaaa atagcgatat cgttacgctt    600 

catgtgccgc tcaatacgga tacgcactat attatcagcc acgaacaaat acagagaatg    660 

aagcaaggag catttcttat caatactggg cgcggtccac ttgtagatac ctatgagttg    720 

gttaaagcat tagaaaacgg gaaactgggc ggtgccgcat tggatgtatt ggaaggagag    780 

gaagagtttt tctactctga ttgcacccaa aaaccaattg ataatcaatt tttacttaaa    840 

cttcaaagaa tgcctaacgt gataatcaca ccgcatacgg cctattatac cgagcaagcg    900 

ttgcgtgata ccgttgaaaa aaccattaaa aactgtttgg attttgaaag gagacaggag    960 

catgaataga ataaaagttg caatactgtt tgggggttgc tcagaggagc atgacgtatc   1020 

ggtaaaatct gcaatagaga tagccgctaa cattaataaa gaaaaatacg agccgttata   1080 

cattggaatt acgaaatctg gtgtatggaa aatgtgcgaa aaaccttgcg cggaatggga   1140 

aaacgacaat tgctattcag ctgtactctc gccggataaa aaaatgcacg gattacttgt   1200 

taaaaagaac catgaatatg aaatcaacca tgttgatgta gcattttcag ctttgcatgg   1260 

caagtcaggt gaagatggat ccatacaagg tctgtttgaa ttgtccggta tcccttttgt   1320 

aggctgcgat attcaaagct cagcaatttg tatggacaaa tcgttgacat acatcgttgc   1380 

gaaaaatgct gggatagcta ctcccgcctt ttgggttatt aataaagatg ataggccggt   1440 

ggcagctacg tttacctatc ctgtttttgt taagccggcg cgttcaggct catccttcgg   1500 

tgtgaaaaaa gtcaatagcg cggacgaatt ggactacgca attgaatcgg caagacaata   1560 

tgacagcaaa atcttaattg agcaggctgt ttcgggctgt gaggtcggtt gtgcggtatt   1620 

gggaaacagt gccgcgttag ttgttggcga ggtggaccaa atcaggctgc agtacggaat   1680 

ctttcgtatt catcaggaag tcgagccgga aaaaggctct gaaaacgcag ttataaccgt   1740 

tcccgcagac ctttcagcag aggagcgagg acggatacag gaaacggcaa aaaaaatata   1800 

taaagcgctc ggctgtagag gtctagcccg tgtggatatg tttttacaag ataacggccg   1860 

cattgtactg aacgaagtca atactctgcc cggtttcacg tcatacagtc gttatccccg   1920 

tatgatggcc gctgcaggta ttgcacttcc cgaactgatt gaccgcttga tcgtattagc   1980 

gttaaagggg tgataagcat ggaaatagga tttacttttt tagatgaaat agtacacggt   2040 

gttcgttggg acgctaaata tgccacttgg gataatttca ccggaaaacc ggttgacggt   2100 

tatgaagtaa atcgcattgt agggacatac gagttggctg aatcgctttt gaaggcaaaa   2160 

gaactggctg ctacccaagg gtacggattg cttctatggg acggttaccg tcctaagcgt   2220 

gctgtaaact gttttatgca atgggctgca cagccggaaa ataacctgac aaaggaaagt   2280 

tattatccca atattgaccg aactgagatg atttcaaaag gatacgtggc ttcaaaatca   2340 

agccatagcc gcggcagtgc cattgatctt acgctttatc gattagacac gggtgagctt   2400 

gtaccaatgg ggagccgatt tgattttatg gatgaacgct ctcatcatgc ggcaaatgga   2460 

atatcatgca atgaagcgca aaatcgcaga cgtttgcgct ccatcatgga aaacagtggg   2520 

tttgaagcat atagcctcga atggtggcac tatgtattaa gagacgaacc ataccccaat   2580 

agctattttg atttccccgt taaataa                                       2607 

 
           
             171  
             1288  
             DNA  
             Pseudomonas aeruginosa  
           
            171 

ggatccatca ggcaacgacg ggctgctgcc ggccatcagc ggacgcaggg aggactttcc     60 

gcaaccggcc gttcgatgcg gcaccgatgg ccttcgcgca ggggtagtga atccgccagg    120 

attgacttgc gctgccctac ctctcactag tgaggggcgg cagcgcatca agcggtgagc    180 

gcactccggc accgccaact ttcagcacat gcgtgtaaat catcgtcgta gagacgtcgg    240 

aatggccgag cagatcctgc acggttcgaa tgtcgtaacc gctgcggagc aaggccgtcg    300 

cgaacgagtg gcggagggtg tgcggtgtgg cgggcttcgt gatgcctgct tgttctacgg    360 

cacgtttgaa ggcgcgctga aaggtctggt catacatgtg atggcgacgc acgacaccgc    420 

tccgtggatc ggtcgaatgc gtgtgctgcg caaaaaccca gaaccacggc caggaatgcc    480 

cggcgcgcgg atacttccgc tcaagggcgt cgggaagcgc aacgccgctg cggccctcgg    540 

cctggtcctt cagccaccat gcccgtgcac gcgacagctg ctcgcgcagg ctgggtgcca    600 

agctctcggg taacatcaag gcccgatcct tggagccctt gccctcccgc acgatgatcg    660 

tgccgtgatc gaaatccaga tccttgaccc gcagttgcaa accctcactg atccgcatgc    720 

ccgttccata cagaagctgg gcgaacaaac gatgctcgcc ttccagaaaa ccgaggatgc    780 

gaaccacttc atccggggtc agcaccaccg gcaagcgccg cgacggccga ggtcttccga    840 

tctcctgaag ccagggcaga tccgtgcaca gcaccttgcc gtagaagaac agcaaggccg    900 

ccaatgcctg acgatgcgtg gagaccgaaa ccttgcgctc gttcgccagc caggacagaa    960 

atgcctcgac ttcgctgctg cccaaggttg ccgggtgacg cacaccgtgg aaacggatga   1020 

aggcacgaac ccagtggaca taagcctgtt cggttcgtaa gctgtaatgc aagtagcgta   1080 

tgcgctcacg caactggtcc agaaccttga ccgaacgcag cggtggtaac ggcgcagtgg   1140 

cggttttcat ggcttgttat gactgttttt ttgtacagtc tatgcctcgg gcatccaagc   1200 

agcaagcgcg ttacgccgtg ggtcgatgtt tgatgttatg gagcagcaac gatgttacgc   1260 

agcagggcag tcgccctaaa acaaagtt                                      1288 

 
           
             172  
             1650  
             DNA  
             Pseudomonas aeruginosa  
           
            172 

gttagatgca ctaagcacat aattgctcac agccaaacta tcaggtcaag tctgctttta     60 

ttatttttaa gcgtgcataa taagccctac acaaattggg agatatatca tgaaaggctg    120 

gctttttctt gttatcgcaa tagttggcga agtaatcgca acatccgcat taaaatctag    180 

cgagggcttt actaagcttg ccccttccgc cgttgtcata atcggttatg gcatcgcatt    240 

ttattttctt tctctggttc tgaaatccat ccctgtcggt gttgcttatg cagtctggtc    300 

gggactcggc gtcgtcataa ttacagccat tgcctggttg cttcatgggc aaaagcttga    360 

tgcgtggggc tttgtaggta tggggctcat aattgctgcc tttttgctcg cccgatcccc    420 

atcgtggaag tcgctgcgga ggccgacgcc atggtgacgg tgttcggcat tctgaatctc    480 

accgaggact ccttcttcga tgagagccgg cggctagacc ccgccggcgc tgtcaccgcg    540 

gcgatcgaaa tgctgcgagt cggatcagac gtcgtggatg tcggaccggc cgccagccat    600 

ccggacgcga ggcctgtatc gccggccgat gagatcagac gtattgcgcc gctcttagac    660 

gccctgtccg atcagatgca ccgtgtttca atcgacagct tccaaccgga aacccagcgc    720 

tatgcgctca agcgcggcgt gggctacctg aacgatatcc aaggatttcc tgaccctgcg    780 

ctctatcccg atattgctga ggcggactgc aggctggtgg ttatgcactc agcgcagcgg    840 

gatggcatcg ccacccgcac cggtcacctt cgacccgaag acgcgctcga cgagattgtg    900 

cggttcttcg aggcgcgggt ttccgccttg cgacggagcg gggtcgctgc cgaccggctc    960 

atcctcgatc cggggatggg atttttcttg agccccgcac cggaaacatc gctgcacgtg   1020 

ctgtcgaacc ttcaaaagct gaagtcggcg ttggggcttc cgctattggt ctcggtgtcg   1080 

cggaaatcct tcttgggcgc caccgttggc cttcctgtaa aggatctggg tccagcgagc   1140 

cttgcggcgg aacttcacgc gatcggcaat ggcgctgact acgtccgcac ccacgcgcct   1200 

ggagatctgc gaagcgcaat caccttctcg gaaaccctcg cgaaatttcg cagtcgcgac   1260 

gccagagacc gagggttaga tcatgcctag cattcacctt ccggccgccc gctagcggac   1320 

cctggtcagg ttccgcgaag gtgggcgcag acatgctggg ctcgtcagga tcaaactgca   1380 

ctatgaggcg gcggttcata ccgcgccagg ggagcgaatg gacagcgagg agcctccgaa   1440 

cgttcgggtc gcctgctcgg gtgatatcga cgaggttgtg cggctgatgc acgacgctgc   1500 

ggcgtggatg tccgccaagg gaacgcccgc ctgggacgtc gcgcggatcg accggacatt   1560 

cgcggagacc ttcgtcctga gatccgagct cctagtcgcg agttgcagcg acggcatcgt   1620 

cggctgttgc accttgtcgg ccgaggatcc                                    1650 

 
           
             173  
             630  
             DNA  
             Enterococcus faecium  
           
            173 

atgggtccga atcctatgaa aatgtatcct atagaaggaa acaaatcagt acaatttatc     60 

aaacctattt tagaaaaatt agaaaatgtt gaggttggag aatactcata ttatgattct    120 

aagaatggag aaacttttga taagcaaatt ttatatcatt atccaatctt aaacgataag    180 

ttaaaaatag gtaaattttg ctcaatagga ccaggtgtaa ctattattat gaatggagca    240 

aatcatagaa tggatggctc aacatatcca tttaatttat ttggtaatgg atgggagaaa    300 

catatgccaa aattagatca actacctatt aagggggata caataatagg taatgatgta    360 

tggataggaa aagatgttgt aattatgcca ggagtaaaaa tcggggatgg tgcaatagta    420 

gctgctaatt ctgttgttgt aaaagatata gcgccataca tgttagctgg aggaaatcct    480 

gctaacgaaa taaaacaaag atttgatcaa gatacaataa atcagctgct tgatataaaa    540 

tggtggaatt ggccaataga cattattaat gagaatatag ataaaattct tgataatagc    600 

atcattagag aagtcatatg gaaaaaatga                                     630 

 
           
             174  
             1440  
             DNA  
             Enterococcus faecalis  
           
            174 

atgaatatag ttgaaaatga aatatgtata agaactttaa tagatgatga ttttcctttg     60 

atgttaaaat ggttaactga tgaaagagta ttagaatttt atggtggtag agataaaaaa    120 

tatacattag aatcattaaa aaaacattat acagagcctt gggaagatga agtttttaga    180 

gtaattattg aatataacaa tgttcctatt ggatatggac aaatatataa aatgtatgat    240 

gagttatata ctgattatca ttatccaaaa actgatgaga tagtctatgg tatggatcaa    300 

tttataggag agccaaatta ttggagtaaa ggaattggta caagatatat taaattgatt    360 

tttgaatttt tgaaaaaaga aagaaatgct aatgcagtta ttttagaccc tcataaaaat    420 

aatccaagag caataagggc ataccaaaaa tctggtttta gaattattga agatttgcca    480 

gaacatgaat tacacgaggg caaaaaagaa gattgttatt taatggaata tagatatgat    540 

gataatgcca caaatgttaa ggcaatgaaa tatttaattg agcattactt tgataatttc    600 

aaagtagata gtattgaaat aatcggtagt ggttatgata gtgtggcata tttagttaat    660 

aatgaataca tttttaaaac aaaatttagt actaataaga aaaaaggtta tgcaaaagaa    720 

aaagcaatat ataatttttt aaatacaaat ttagaaacta atgtaaaaat tcctaatatt    780 

gaatattcgt atattagtga tgaattatct atactaggtt ataaagaaat taaaggaact    840 

tttttaacac cagaaattta ttctactatg tcagaagaag aacaaaattt gttaaaacga    900 

gatattgcca gttttttaag acaaatgcac ggtttagatt atacagatat tagtgaatgt    960 

actattgata ataaacaaaa tgtattagaa gagtatatat tgttgcgtga aactatttat   1020 

aatgatttaa ctgatataga aaaagattat atagaaagtt ttatggaaag actaaatgca   1080 

acaacagttt ttgagggtaa aaagtgttta tgccataatg attttagttg taatcatcta   1140 

ttgttagatg gcaataatag attaactgga ataattgatt ttggagattc tggaattata   1200 

gatgaatatt gtgattttat atacttactt gaagatagtg aagaagaaat aggaacaaat   1260 

tttggagaag atatattaag aatgtatgga aatatagata ttgagaaagc aaaagaatat   1320 

caagatatag ttgaagaata ttatcctatt gaaactattg tttatggaat taaaaatatt   1380 

aaacaggaat ttatcgaaaa tggtagaaaa gaaatttata aaaggactta taaagattga   1440 

 
           
             175  
             660  
             DNA  
             Staphylococcus aureus  
           
            175 

ttgaatttaa acaatgacca tggacctgat cccgaaaata ttttaccgat aaaagggaat     60 

cggaatcttc aatttataaa acctactata acgaacgaaa acattttggt gggggaatat    120 

tcttattatg atagtaagcg aggagaatcc tttgaagatc aagtcttata tcattatgaa    180 

gtgattggag ataagttgat tataggaaga ttttgttcaa ttggtcccgg aacaacattt    240 

attatgaatg gtgcaaacca tcggatggat ggatcaacat atccttttca tctattcagg    300 

atgggttggg agaagtatat gccttcctta aaagatcttc ccttgaaagg ggacattgaa    360 

attggaaatg atgtatggat aggtagagat gtaaccatta tgcctggggt gaaaattggg    420 

gacggggcaa tcattgctgc agaagctgtt gtcacaaaga atgttgctcc ctattctatt    480 

gtcggtggaa atcccttaaa atttataaga aaaaggtttt ctgatggagt tatcgaagaa    540 

tggttagctt tacaatggtg gaatttagat atgaaaatta ttaatgaaaa tcttcccttc    600 

ataataaatg gagatatcga aatgctgaag agaaaaagaa aacttctaga tgacacttga    660 

 
           
             176  
             1569  
             DNA  
             Staphylococcus aureus  
           
            176 

atgaaaataa tgttagaggg acttaatata aaacattatg ttcaagatcg tttattgttg     60 

aacataaatc gcctaaagat ttatcagaat gatcgtattg gtttaattgg taaaaatgga    120 

agtggaaaaa caacgttact tcacatatta tataaaaaaa ttgtgcctga agaaggtatt    180 

gtaaaacaat tttcacattg tgaacttatt cctcaattga agctcataga atcaactaaa    240 

agtggtggtg aagtaacacg aaactatatt cggcaagcgc ttgataaaaa tccagaactg    300 

ctattagcag atgaaccaac aactaactta gataataact atatagaaaa attagaacag    360 

gatttaaaaa attggcatgg agcatttatt atagtttcac atgatcgcgc ttttttagat    420 

aacttgtgta ctactatatg ggaaattgac gagggaagaa taactgaata taaggggaat    480 

tatagtaact atgttgaaca aaaagaatta gaaagacatc gagaagaatt agaatatgaa    540 

aaatatgaaa aagaaaagaa acgattggaa aaagctataa atataaaaga acagaaagct    600 

caacgagcaa ctaaaaaacc gaaaaactta agtttatctg aaggcaaaat aaaaggagca    660 

aagccatact ttgcaggtaa gcaaaagaag ttacgaaaaa ctgtaaaatc tctagaaacc    720 

agactagaaa aacttgaaag cgtcgaaaag agaaacgaac ttcctccact taaaatggat    780 

ttagtgaact tagaaagtgt aaaaaataga actataatac gtggtgaaga tgtctcgggt    840 

acaattgaag gacgggtatt gtggaaagca aaaagtttta gtattcgcgg aggagacaag    900 

atggcaatta tcggatctaa tggtacagga aagacaacgt ttattaaaaa aattgtgcat    960 

gggaatcctg gtatttcatt atcgccatct gtcaaaatcg gttattttag ccaaaaaata   1020 

gatacattag aattagataa gagcatttta gaaaatgttc aatcttcttc acaacaaaat   1080 

gaaactctta ttcgaactat tctagctaga atgcattttt ttagagatga tgtttataaa   1140 

ccaataagtg tcttaagtgg tggagagcga gttaaagtag cactaactaa agtattctta   1200 

agtgaagtta atacgttggt actagatgaa ccaacaaact ttcttgatat ggaagctata   1260 

gaggcgtttg aatctttgtt aaaggaatat aatggcagta taatctttgt atctcacgat   1320 

cgtaaattta tcgaaaaagt agccactcga ataatgacaa ttgataataa agaaataaaa   1380 

atatttgatg gcacatatga acaatttaaa caagctgaaa agccaacaag gaatattaaa   1440 

gaagataaaa aacttttact tgagacaaaa attacagaag tactcagtcg attgagtatt   1500 

gaaccttcgg aagaattaga acaagagttt caaaacttaa taaatgaaaa aagaaatttg   1560 

gataaataa                                                           1569 

 
           
             177  
             1467  
             DNA  
             Staphylococcus epidermidis  
           
            177 

atggaacaat atacaattaa atttaaccaa atcaatcata aattgacaga tttacgatca     60 

cttaacatcg atcatcttta tgcttaccaa tttgaaaaaa tagcacttat tgggggtaat    120 

ggtactggta aaaccacatt actaaatatg attgctcaaa aaacaaaacc agaatctgga    180 

acagttgaaa cgaatggcga aattcaatat tttgaacagc ttaacatgga tgtggaaaat    240 

gattttaaca cgttagacgg tagtttaatg agtgaactcc atatacctat gcatacaacc    300 

gacagtatga gtggtggtga aaaagcaaaa tataaattac gtaatgtcat atcaaattat    360 

agtccgatat tacttttaga tgaacctaca aatcacttgg ataaaattgg taaagattat    420 

ctgaataata ttttaaaata ttactatggt actttaatta tagtaagtca cgatagagca    480 

cttatagacc aaattgctga cacaatttgg gatatacaag aagatggcac aataagagtg    540 

tttaaaggta attacacaca gtatcaaaat caatatgaac aagaacagtt agaacaacaa    600 

cgtaaatatg aacagtatat aagtgaaaaa caaagattgt cccaagccag taaagctaaa    660 

cgaaatcaag cgcaacaaat ggcacaagca tcatcaaaac aaaaaaataa aagtatagca    720 

ccagatcgtt taagtgcatc aaaagaaaaa ggcacggttg agaaggctgc tcaaaaacaa    780 

gctaagcata ttgaaaaaag aatggaacat ttggaagaag ttgaaaaacc acaaagttat    840 

catgaattca attttccaca aaataaaatt tatgatatcc ataataatta tccaatcatt    900 

gcacaaaatc taacattggt taaaggaagt caaaaactgc taacacaagt acgattccaa    960 

ataccatatg gcaaaaatat agcgctcgta ggtgcaaatg gtgtaggtaa gacaacttta   1020 

cttgaagcta tttaccacca aatagaggga attgattgtt ctcctaaagt gcaaatggca   1080 

tactatcgtc aacttgctta tgaagacatg cgtgacgttt cattattgca atatttaatg   1140 

gatgaaacgg attcatcaga atcattcagt agagctattt taaataactt gggtttaaat   1200 

gaagcacttg agcgttcttg taatgttttg agtggtgggg aaagaacgaa attatcgtta   1260 

gcagtattat tttcaacgaa agcgaatatg ttaattttgg atgaaccaac taatttttta   1320 

gatattaaaa cattagaagc attagaaatg tttatgaata aatatcctgg aatcattttg   1380 

tttacatcac atgatacaag gtttgttaaa catgtatcag ataaaaaatg ggaattaaca   1440 

ggacaatcta ttcatgatat aacttaa                                       1467