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Bacterial pathogenomics

Nature volume 449, pages 835–842 (2007)Cite this article

Abstract

Genomes from all of the crucial bacterial pathogens of humans, plants and animals have now been sequenced, as have genomes from many of the important commensal, symbiotic and environmental microorganisms. Analysis of these sequences has revealed the forces that shape pathogen evolution and has brought to light unexpected aspects of pathogen biology. The finding that horizontal gene transfer and genome decay have key roles in the evolution of bacterial pathogens was particularly surprising. It has also become evident that even the definitions for 'pathogen' and 'virulence factor' need to be re-evaluated.

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Figure 1: Bacterial genome dynamics.
Figure 2: The eco–evo view of bacterial pathogenomics.

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References

  1. Read, T. D. et al. Comparative genome sequencing for discovery of novel polymorphisms in Bacillus anthracis . Science 296, 2028–2033 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Tettelin, H. et al. Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial 'pan-genome'. Proc. Natl Acad. Sci. USA 102, 13950–13955 (2005).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hayashi, T. et al. Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12. DNA Res. 8, 11–22 (2001); erratum 8, 96 (2001).

    Article  CAS  PubMed  Google Scholar 

  4. Kuroda, M. et al. Whole genome sequencing of meticillin-resistant Staphylococcus aureus . Lancet 357, 1225–1240 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Fraser-Liggett, C. M. Insights on biology and evolution from microbial genome sequencing. Genome Res. 15, 1603–1610 (2005).

    Article  CAS  PubMed  Google Scholar 

  6. Lawrence, J. G. Horizontal and vertical gene transfer: the life history of pathogens. Contrib. Microbiol. 12, 255–271 (2005).

    Article  CAS  PubMed  Google Scholar 

  7. Raskin, D. M., Seshadri, R., Pukatzki, S. U. & Mekalanos, J. J. Bacterial genomics and pathogen evolution. Cell 124, 703–714 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Wren, B. W. The yersiniae — a model genus to study the rapid evolution of bacterial pathogens. Nature Rev. Microbiol. 1, 55–64 (2003).

    Article  CAS  Google Scholar 

  9. Pearson, T. et al. Phylogenetic discovery bias in Bacillus anthracis using single-nucleotide polymorphisms from whole-genome sequencing. Proc. Natl Acad. Sci. USA 101, 13536–13541 (2004).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  10. Touchman, J. W. et al. A North American Yersinia pestis draft genome aequence: SNPs and phylogenetic analysis. PLoS ONE 2, e220 (2007).

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  11. Gutacker, M. M. et al. Genome-wide analysis of synonymous single nucleotide polymorphisms in Mycobacterium tuberculosis complex organisms: resolution of genetic relationships among closely related microbial strains. Genetics 162, 1533–1543 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Monot, M. et al. On the origin of leprosy. Science 308, 1040–1042 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

  13. Hayashi, K. et al. Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol. Syst. Biol. 2, doi:10.1038/msb4100049 (2006).

  14. Zhang, W. et al. Probing genomic diversity and evolution of Escherichia coli O157 by single nucleotide polymorphisms. Genome Res. 16, 757–767 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chaudhuri, R. R. et al. Genome sequencing shows that European isolates of Francisella tularensis subspecies tularensis are almost identical to US laboratory strain Schu S4. PLoS ONE 2, e352 (2007).

    Article  ADS  PubMed  PubMed Central  CAS  Google Scholar 

  16. Shendure, J. et al. Accurate multiplex polony sequencing of an evolved bacterial genome. Science 309, 1728–1732 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Romero, C. M. et al. Genome sequence alterations detected upon passage of Burkholderia mallei ATCC 23344 in culture and in mammalian hosts. BMC Genomics 7, 228 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Moxon, R., Bayliss, C. & Hood, D. Bacterial contingency loci: the role of simple sequence DNA repeats in bacterial adaptation. Annu. Rev. Genet. 40, 307–333 (2006).

    Article  CAS  PubMed  Google Scholar 

  19. van der Woude, M. W. & Baumler, A. J. Phase and antigenic variation in bacteria. Clin. Microbiol. Rev. 17, 581–611 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Parkhill, J. et al. The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences. Nature 403, 665–668 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  21. Cerdeno-Tarraga, A. M. et al. Extensive DNA inversions in the B. fragilis genome control variable gene expression. Science 307, 1463–1465 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

  22. Medini, D., Donati, C., Tettelin, H., Masignani, V. & Rappuoli, R. The microbial pan-genome. Curr. Opin. Genet. Dev. 15, 589–594 (2005).

    Article  CAS  PubMed  Google Scholar 

  23. Cole, S. T. et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393, 537–544 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  24. Bruggemann, H., Cazalet, C. & Buchrieser, C. Adaptation of Legionella pneumophila to the host environment: role of protein secretion, effectors and eukaryotic-like proteins. Curr. Opin. Microbiol. 9, 86–94 (2006).

    Article  PubMed  CAS  Google Scholar 

  25. Salanoubat, M. et al. Genome sequence of the plant pathogen Ralstonia solanacearum . Nature 415, 497–502 (2002).

    Article  CAS  PubMed  Google Scholar 

  26. Turner, S. M. et al. Phylogenetic comparisons reveal multiple acquisitions of the toxin genes by enterotoxigenic Escherichia coli strains of different evolutionary lineages. J. Clin. Microbiol. 44, 4528–4536 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Freeman, V. J. Studies on the virulence of bacteriophage-infected strains of Corynebacterium diphtheriae . J. Bacteriol. 61, 675–688 (1951).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Brussow, H., Canchaya, C. & Hardt, W. D. Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion. Microbiol. Mol. Biol. Rev. 68, 560–602 (2004).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Tobe, T. et al. An extensive repertoire of type III secretion effectors in Escherichia coli O157 and the role of lambdoid phages in their dissemination. Proc. Natl Acad. Sci. USA 103, 14941–14946 (2006).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ohnishi, M., Kurokawa, K. & Hayashi, T. Diversification of Escherichia coli genomes: are bacteriophages the major contributors? Trends Microbiol. 9, 481–485 (2001).

    Article  CAS  PubMed  Google Scholar 

  31. Hendrix, R. W., Lawrence, J. G., Hatfull, G. F. & Casjens, S. The origins and ongoing evolution of viruses. Trends Microbiol. 8, 504–508 (2000).

    Article  CAS  PubMed  Google Scholar 

  32. Dobrindt, U., Hochhut, B., Hentschel, U. & Hacker, J. Genomic islands in pathogenic and environmental microorganisms. Nature Rev. Microbiol. 2, 414–424 (2004).

    Article  CAS  Google Scholar 

  33. Zhang, L. et al. Regulators encoded in the Escherichia coli type III secretion system 2 gene cluster influence expression of genes within the locus for enterocyte effacement in enterohemorrhagic E. coli O157:H7. Infect. Immun. 72, 7282–7293 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Nakanishi, N. et al. ppGpp with DksA controls gene expression in the locus of enterocyte effacement (LEE) pathogenicity island of enterohaemorrhagic Escherichia coli through activation of two virulence regulatory genes. Mol. Microbiol. 61, 194–205 (2006).

    Article  CAS  PubMed  Google Scholar 

  35. Laaberki, M. H., Janabi, N., Oswald, E. & Repoila, F. Concert of regulators to switch on LEE expression in enterohemorrhagic Escherichia coli O157:H7: interplay between Ler, GrlA, HNS and RpoS. Int. J. Med. Microbiol. 296, 197–210 (2006).

    Article  CAS  PubMed  Google Scholar 

  36. Ren, C. P. et al. The ETT2 gene cluster, encoding a second type III secretion system from Escherichia coli, is present in the majority of strains but has undergone widespread mutational attrition. J. Bacteriol. 186, 3547–3560 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Mira, A., Ochman, H. & Moran, N. A. Deletional bias and the evolution of bacterial genomes. Trends Genet. 17, 589–596 (2001).

    Article  CAS  PubMed  Google Scholar 

  38. Ren, C. P., Beatson, S. A., Parkhill, J. & Pallen, M. J. The Flag-2 locus, an ancestral gene cluster, is potentially associated with a novel flagellar system from Escherichia coli . J. Bacteriol. 187, 1430–1440 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Cole, S. T. et al. Massive gene decay in the leprosy bacillus. Nature 409, 1007–1011 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  40. Parkhill, J. et al. Genome sequence of Yersinia pestis, the causative agent of plague. Nature 413, 523–527 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  41. Parkhill, J. et al. Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18. Nature 413, 848–852 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  42. Siguier, P., Filee, J. & Chandler, M. Insertion sequences in prokaryotic genomes. Curr. Opin. Microbiol. 9, 526–531 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. Wernegreen, J. J. For better or worse: genomic consequences of intracellular mutualism and parasitism. Curr. Opin. Genet. Dev. 15, 572–583 (2005).

    Article  CAS  PubMed  Google Scholar 

  44. Andersson, S. G. et al. The genome sequence of Rickettsia prowazekii and the origin of mitochondria. Nature 396, 133–140 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  45. Perez-Brocal, V. et al. A small microbial genome: the end of a long symbiotic relationship? Science 314, 312–313 (2006).

    Article  ADS  CAS  PubMed  Google Scholar 

  46. Nakabachi, A. et al. The 160-kilobase genome of the bacterial endosymbiont Carsonella . Science 314, 267 (2006).

    Article  CAS  PubMed  Google Scholar 

  47. Anderson, S. et al. Sequence and organization of the human mitochondrial genome. Nature 290, 457–465 (1981).

    Article  ADS  CAS  PubMed  Google Scholar 

  48. West, N. P. et al. Optimization of virulence functions through glucosylation of Shigella LPS. Science 307, 1313–1317 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

  49. Maurelli, A. T. Black holes, antivirulence genes, and gene inactivation in the evolution of bacterial pathogens. FEMS Microbiol. Lett. 267, 1–8 (2007).

    Article  CAS  PubMed  Google Scholar 

  50. Leatham, M. P. et al. Mouse intestine selects nonmotile flhDC mutants of Escherichia coli MG1655 with increased colonizing ability and better utilization of carbon sources. Infect. Immun. 73, 8039–8049 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Fux, C. A., Shirtliff, M., Stoodley, P. & Costerton, J. W. Can laboratory reference strains mirror 'real-world' pathogenesis? Trends Microbiol. 13, 58–63 (2005).

    Article  CAS  PubMed  Google Scholar 

  52. Hobman, J. L., Penn, C. W. & Pallen, M. J. Laboratory strains of Escherichia coli: model citizens or deceitful delinquents growing old disgracefully? Mol. Microbiol. 64, 881–885 (2007).

    Article  CAS  PubMed  Google Scholar 

  53. Achtman, M. et al. Microevolution and history of the plague bacillus, Yersinia pestis . Proc. Natl Acad. Sci. USA 101, 17837–17842 (2004).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  54. Achtman, M. et al. Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis . Proc. Natl Acad. Sci. USA 96, 14043–14048 (1999).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  55. van der Woude, M. W. Re-examining the role and random nature of phase variation. FEMS Microbiol. Lett. 254, 190–197 (2006).

    Article  CAS  PubMed  Google Scholar 

  56. Wick, L. M., Qi, W., Lacher, D. W. & Whittam, T. S. Evolution of genomic content in the stepwise emergence of Escherichia coli O157:H7. J. Bacteriol. 187, 1783–1791 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Rendón, M. A. et al. Commensal and pathogenic Escherichia coli use a common pilus adherence factor for epithelial cell colonization. Proc. Natl Acad. Sci. USA 104, 10637–10642 (2007).

    Article  ADS  PubMed  CAS  PubMed Central  Google Scholar 

  58. Sheng, H., Lim, J. Y., Knecht, H. J., Li, J. & Hovde, C. J. Role of Escherichia coli O157:H7 virulence factors in colonization at the bovine terminal rectal mucosa. Infect. Immun. 74, 4685–4693 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Meltz Steinberg, K. & Levin, B. R. Grazing protozoa and the evolution of the Escherichia coli O157:H7 Shiga toxin-encoding prophage. Proc. R. Soc. B 274, 1921–1929 (2007).

    Article  PubMed Central  Google Scholar 

  60. Albert-Weissenberger, C., Cazalet, C. & Buchrieser, C. Legionella pneumophila — a human pathogen that co-evolved with fresh water protozoa. Cell. Mol. Life Sci. 64, 432–448 (2007).

    Article  CAS  PubMed  Google Scholar 

  61. Hall, N. Advanced sequencing technologies and their wider impact in microbiology. J. Exp. Biol. 210, 1518–1525 (2007).

    Article  CAS  PubMed  Google Scholar 

  62. Field, D., Wilson, G. & van der Gast, C. How do we compare hundreds of bacterial genomes? Curr. Opin. Microbiol. 9, 499–504 (2006).

    Article  CAS  PubMed  Google Scholar 

  63. Rusch, D. B. et al. The Sorcerer II Global Ocean Sampling Expedition: Northwest Atlantic through Eastern Tropical Pacific. PLoS Biol. 5, e77 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Gill, S. R. et al. Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359 (2006).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  65. Brogden, K. A., Guthmiller, J. M. & Taylor, C. E. Human polymicrobial infections. Lancet 365, 253–255 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Meyers, L. A., Levin, B. R., Richardson, A. R. & Stojiljkovic, I. Epidemiology, hypermutation, within-host evolution and the virulence of Neisseria meningitidis . Proc. R. Soc. B 270, 1667–1677 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Pallen, M. J., Beatson, S. A. & Bailey, C. M. Bioinformatics, genomics and evolution of non-flagellar type-III secretion systems: a Darwinian perspective. FEMS Microbiol. Rev. 29, 201–229 (2005).

    Article  CAS  PubMed  Google Scholar 

  68. Ffrench-Constant, R. H. et al. A genomic sample sequence of the entomopathogenic bacterium Photorhabdus luminescens W14: potential implications for virulence. Appl. Environ. Microbiol. 66, 3310–3329 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Moran, N. A., Degnan, P. H., Santos, S. R., Dunbar, H. E. & Ochman, H. The players in a mutualistic symbiosis: insects, bacteria, viruses, and virulence genes. Proc. Natl Acad. Sci. USA 102, 16919–16926 (2005).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  70. Silver, A. C. et al. Interaction between innate immune cells and a bacterial type III secretion system in mutualistic and pathogenic associations. Proc. Natl Acad. Sci. USA 104, 9481–9486 (2007).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  71. Skorpil, P. et al. NopP, a phosphorylated effector of Rhizobium sp. strain NGR234, is a major determinant of nodulation of the tropical legumes Flemingia congesta and Tephrosia vogelii . Mol. Microbiol. 57, 1304–1317 (2005).

    Article  CAS  PubMed  Google Scholar 

  72. Horn, M. et al. Illuminating the evolutionary history of chlamydiae. Science 304, 728–730 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  73. Dale, C., Young, S. A., Haydon, D. T. & Welburn, S. C. The insect endosymbiont Sodalis glossinidius utilizes a type III secretion system for cell invasion. Proc. Natl Acad. Sci. USA 98, 1883–1888 (2001).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  74. Pukatzki, S. et al. Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system. Proc. Natl Acad. Sci. USA 103, 1528–1533 (2006).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  75. Mougous, J. D. et al. A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science 312, 1526–1530 (2006).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  76. Pym, A. S., Brodin, P., Brosch, R., Huerre, M. & Cole, S. T. Loss of RD1 contributed to the attenuation of the live tuberculosis vaccines Mycobacterium bovis BCG and Mycobacterium microti . Mol. Microbiol. 46, 709–717 (2002).

    Article  CAS  PubMed  Google Scholar 

  77. Lewis, K. N. et al. Deletion of RD1 from Mycobacterium tuberculosis mimics bacille Calmette–Guerin attenuation. J. Infect. Dis. 187, 117–123 (2003).

    Article  PubMed  Google Scholar 

  78. Brodin, P. et al. Dissection of ESAT-6 system 1 of Mycobacterium tuberculosis and impact on immunogenicity and virulence. Infect. Immun. 74, 88–98 (2006).

    Article  MathSciNet  CAS  PubMed  PubMed Central  Google Scholar 

  79. Pallen, M. J. The ESAT-6/WXG100 superfamily — and a new Gram-positive secretion system? Trends Microbiol. 10, 209–212 (2002).

    Article  CAS  PubMed  Google Scholar 

  80. Desvaux, M. et al. Genomic analysis of the protein secretion systems in Clostridium acetobutylicum ATCC 824. Biochim. Biophys. Acta 1745, 223–253 (2005).

    Article  CAS  PubMed  Google Scholar 

  81. Burts, M. L., Williams, W. A., DeBord, K. & Missiakas, D. M. EsxA and EsxB are secreted by an ESAT-6-like system that is required for the pathogenesis of Staphylococcus aureus infections. Proc. Natl Acad. Sci. USA 102, 1169–1174 (2005).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  82. Huang, S. H. et al. Identification and characterization of an Escherichia coli invasion gene locus, ibeB, required for penetration of brain microvascular endothelial cells. Infect. Immun. 67, 2103–2109 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Huang, S. H., Stins, M. F. & Kim, K. S. Bacterial penetration across the blood–brain barrier during the development of neonatal meningitis. Microbes Infect. 2, 1237–1244 (2000).

    Article  CAS  PubMed  Google Scholar 

  84. Huang, S. H., Wan, Z. S., Chen, Y. H., Jong, A. Y. & Kim, K. S. Further characterization of Escherichia coli brain microvascular endothelial cell invasion gene ibeA by deletion, complementation, and protein expression. J. Infect. Dis. 183, 1071–1078 (2001).

    Article  CAS  PubMed  Google Scholar 

  85. Fleischmann, R. D. et al. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 269, 496–512 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  86. Parkhill, J. The importance of complete genome sequences. Trends Microbiol. 10, 219–220 (2002).

    Article  CAS  PubMed  Google Scholar 

  87. Dorer, M. S. & Isberg, R. R. Non-vertebrate hosts in the analysis of host–pathogen interactions. Microbes Infect. 8, 1637–1646 (2006).

    Article  CAS  PubMed  Google Scholar 

  88. Hilbi, H., Weber, S. S., Ragaz, C., Nyfeler, Y. & Urwyler, S. Environmental predators as models for bacterial pathogenesis. Environ. Microbiol. 9, 563–575 (2007).

    Article  CAS  PubMed  Google Scholar 

  89. Maiden, M. C. Multilocus sequence typing of bacteria. Annu. Rev. Microbiol. 60, 561–588 (2006).

    Article  CAS  PubMed  Google Scholar 

  90. Lindstedt, B. A. Multiple-locus variable number tandem repeats analysis for genetic fingerprinting of pathogenic bacteria. Electrophoresis 26, 2567–2582 (2005).

    Article  CAS  PubMed  Google Scholar 

  91. Dorrell, N., Hinchliffe, S. J. & Wren, B. W. Comparative phylogenomics of pathogenic bacteria by microarray analysis. Curr. Opin. Microbiol. 8, 620–626 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Champion, O. L. et al. Comparative phylogenomics of the food-borne pathogen Campylobacter jejuni reveals genetic markers predictive of infection source. Proc. Natl Acad. Sci. USA 102, 16043–16048 (2005).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  93. Renesto, P. et al. Genome-based design of a cell-free culture medium for Tropheryma whipplei . Lancet 362, 447–449 (2003).

    Article  PubMed  Google Scholar 

  94. Wacker, M. et al. N-linked glycosylation in Campylobacter jejuni and its functional transfer into E. coli . Science 298, 1790–1793 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  95. Mora, M., Donati, C., Medini, D., Covacci, A. & Rappuoli, R. Microbial genomes and vaccine design: refinements to the classical reverse vaccinology approach. Curr. Opin. Microbiol. 9, 532–536 (2006).

    Article  CAS  PubMed  Google Scholar 

  96. Jenner, R. G. & Young, R. A. Insights into host responses against pathogens from transcriptional profiling. Nature Rev. Microbiol. 3, 281–294 (2005).

    Article  CAS  Google Scholar 

  97. Hill, A. V. Aspects of genetic susceptibility to human infectious diseases. Annu. Rev. Genet. 40, 469–486 (2006).

    Article  CAS  PubMed  Google Scholar 

  98. Falkow, S. Molecular Koch's postulates applied to microbial pathogenicity. Rev. Infect. Dis. 10 (suppl. 2), S274–S276 (1988).

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank L. Snyder, J. Kelly, D. Baker, L. Bingle and S. Andersson for critical reading of the manuscript. We acknowledge the Biotechnology and Biological Sciences Research Council for funding numerous genomic research projects in our laboratories, and the Wellcome Trust (particularly the Wellcome Trust Sanger Institute) for facilitating bacterial genome sequencing in the United Kingdom. This article is dedicated to the memory of C. A. Hart.

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Authors and Affiliations

  1. Centre for Systems Biology, University of Birmingham, Birmingham, B15 2TT, UK

    Mark J. Pallen

  2. Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK

    Brendan W. Wren

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Correspondence should be addressed to the authors (m.pallen@bham.ac.uk; brendan.wren@lshtm.ac.uk).

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Pallen, M., Wren, B. Bacterial pathogenomics. Nature 449, 835–842 (2007). https://doi.org/10.1038/nature06248

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