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Molecular Koch's postulates applied to bacterial pathogenicity — a personal recollection 15 years later

Nature Reviews Microbiology volume 2, pages 67–72 (2004)Cite this article

Abstract

Koch's postulates were derived from Robert Koch's work on infectious diseases, such as anthrax and tuberculosis, which still engage us to this day. These guidelines were an attempt to establish a standard for identifying the specific causation of an infectious disease and to convince sceptics that microorganisms could cause disease. They were also established to encourage an increasing number of novice microbiologists to use more rigorous criteria before claiming a causal relationship between a microorganism and a disease.

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Figure 1: The use of gene knockout animals to help determine virulence gene function.
Figure 2: The use of the host response to infection to define the function of bacterial virulence genes.

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References

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

    Article  PubMed  Google Scholar 

  2. Fredricks, D. N. & Relman, D. A. Sequence-based identification of microbial pathogens: A reconsideration of Koch's postulates. Clin. Microbiol. Rev. 9, 18–33 (1996).

    Article  CAS  PubMed  Google Scholar 

  3. Evans, S. Causation and disease: the Henle–Koch postulates revisited. Yale J. Biol. Med. 49, 175–195 (1976).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Casadevall, A. & L. Pirofski, L. Host–pathogen interactions: the attributes of virulence. J. Infect. Dis. 184, 337–344 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. Finlay, B. B. & Falkow, S. Common themes in microbial pathogenicity revisited. Microbiol. Mol. Biol. Rev. 61, 136–169 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Medzhitov, R. & Janeway, C. Jr. Toll receptor family and microbial recognition. Trends Microbiol. 8, 452–456 (2000).

    Article  CAS  PubMed  Google Scholar 

  7. Ozinsky, A. et al. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc. Natl Acad. Sci. USA 97, 13766–137671 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Moxon, E. R., Hood, D. W., Saunders, N. J., Schweda, E. K. & Richards, J. C. Functional genomics of pathogenic bacteria. Philos. Trans. R. Soc. Lond. B Biol. Sci. 357, 109–116 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hacker, J. & Kaper, J. B. Pathogenicity islands and the evolution of microbes. Annu. Rev. Microbiol. 54, 641–679 (2000).

    Article  CAS  PubMed  Google Scholar 

  10. Ochman, H. & Moran, N. A. Genes lost and genes found: evolution of bacterial pathogenesis and symbiosis. Science 292, 1096–1099 (2001).

    Article  CAS  PubMed  Google Scholar 

  11. Camilli, A., Merrell, D. S. & Mekalanos, J. J. in Principles of Bacterial Pathogenesis. (ed. Groismann, E.), 133–177 (Academic Press, New York, 2001).

    Book  Google Scholar 

  12. Alegado, R. A., Campbell, M. C., Chen, W. C., Slutz, S. S. & Tan, M. W. Characterization of mediators of microbial virulence and innate immunity using the Caenorhabditis elegans host-pathogen model. Cell. Microbiol. 5, 435–444 (2003).

    Article  CAS  PubMed  Google Scholar 

  13. Tzou, P., De Gregorio, E. & Lemaitre, B. How Drosophila combats microbial infection: a model to study innate immunity and host–pathogen interactions. Curr. Opin. Microbiol. 5, 102–110 (2002).

    Article  CAS  PubMed  Google Scholar 

  14. Darby, C., Hsu, J. W., Ghori, N. & Falkow, S. Caenorhabditis elegans: plague bacteria biofilm blocks food intake. Nature 417, 243–244 (2002).

    Article  CAS  PubMed  Google Scholar 

  15. Beuzon, C. R. & Holden, D. W. Use of mixed infections with Salmonella strains to study virulence genes and their interactions in vivo. Microbes Infect. 3, 1345–1352 (2001).

    Article  CAS  PubMed  Google Scholar 

  16. Lengeling, A., Pfeffer, K. & Balling, R. The battle of two genomes: genetics of bacterial host/pathogen interactions in mice. Mamm. Genome 12, 261–271 (2001).

    Article  CAS  PubMed  Google Scholar 

  17. Galan, J. E. Salmonella interactions with host cells: type III secretion at work. Annu. Rev. Cell Dev. Biol. 17, 53–86 (2001).

    Article  CAS  PubMed  Google Scholar 

  18. Monack, D. M. et al. Salmonella exploits caspase-1 to colonize Peyer's patches in a murine typhoid model. J. Exp. Med. 192, 249–258 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Jarvelainen, H. A., Galmiche, A. & Zychlinsky, A. Caspase-1 activation by Salmonella. Trends Cell Biol. 13, 204–209 (2003).

    Article  PubMed  Google Scholar 

  20. Monack, D. & Falkow, S. Apoptosis as a common bacterial virulence strategy. Int. J. Med. Microbiol. 290, 7–13 (2000).

    Article  CAS  PubMed  Google Scholar 

  21. Waterman, S. R. & Holden, D. W. Functions and effectors of the Salmonella pathogenicity island 2 type III secretion system. Cell. Microbiol. 5, 501–11 (2003).

    Article  CAS  PubMed  Google Scholar 

  22. Wick, M. J. The role of dendritic cells during Salmonella infection. Curr. Opin. Immunol. 14, 437–143 (2002).

    Article  CAS  PubMed  Google Scholar 

  23. Vidal, S. M., Malo, D., Vogan, K., Skamene, E. & Gros, P. Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. Cell 73, 469–485 (1993).

    Article  CAS  PubMed  Google Scholar 

  24. Monack, D., Bowley, D. M. & Falkow, S. Salmonella typhimurium persists within macrophages in the mesenteric lymph nodes of chronically infected Nramp2+/+ mice and can be reactivated by IFNγ neutralization. J. Exp. Med. (in the press).

  25. Sebastiani, G. et al. Mapping of genetic modulators of natural resistance to infection with Salmonella typhimurium in wild-derived mice. Genomics 47, 180–186 (1998).

    Article  CAS  PubMed  Google Scholar 

  26. Sebastiani, G. et al. Cloning and characterization of the murine toll-like receptor 5 (Tlr5) gene: sequence and mRNA expression studies in Salmonella-susceptible MOLF/Ei mice. Genomics 64, 230–240 (2000).

    Article  CAS  PubMed  Google Scholar 

  27. Cummings, C. A. & Relman, D. Using DNA microarrays to study host–microbe interactions. Emerg. Infect. Dis. 6, 513–525 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Rosenberger, C. M., Pollard, A. J. & Finlay, B. B. Gene array technology to determine host responses to Salmonella. Microbes Infect. 3, 1353–1360 (2001).

    Article  CAS  PubMed  Google Scholar 

  29. Guillemin, K., Salama, N. R., Tompkins, L. S. & Falkow, S. Cag pathogenicity island-specific responses of gastric epithelial cells to Helicobacter pylori infection. Proc. Natl Acad. Sci. USA 99, 15136–15141 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Covacci, A., Telford, J. L., Del Giudice, G., Parsonnet, J. & Rappuoli, R. Helicobacter pylori virulence and genetic geography. Science 284, 1328–1333 (1999).

    Article  CAS  PubMed  Google Scholar 

  31. Higashi, H. et al. SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science 295, 683–686 (2002).

    Article  CAS  PubMed  Google Scholar 

  32. Amieva, M. R., Vogelmann, R., Covacci, A., Tompkins, L. S., Nelson, W. J. & Falkow, S. Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science 300, 1430–1434 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Dudley, N. R. & Goldstein, B. RNA interference: silencing in the cytoplasm and nucleus. Curr. Opin. Mol. Ther. 5, 113–117 (2003).

    CAS  PubMed  Google Scholar 

  34. Hannon, G. J. RNA interference. Nature 418, 244–251 (2002).

    Article  CAS  PubMed  Google Scholar 

  35. Shi, Y. Mammalian RNAi for the masses. Trends Genet. 19, 9–12 (2003).

    Article  PubMed  Google Scholar 

  36. Falkow, S. What is a pathogen? ASM News 63, 359–365 (1997).

    Google Scholar 

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Acknowledgements

I would like to acknowledge D. Monack, I. Brodsky and E. Joyce for reading the manuscript and providing me with their fresh insights about the 'postulates'.

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  1. Stanford University School of Medicine, Stanford, 94305-5124, California, USA

    Stanley Falkow

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  1. Stanley Falkow
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The author declares no competing financial interests.

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Falkow, S. Molecular Koch's postulates applied to bacterial pathogenicity — a personal recollection 15 years later. Nat Rev Microbiol 2, 67–72 (2004). https://doi.org/10.1038/nrmicro799

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