Enterohaemorrhagic E. coli (EHEC) and enteropathogenic E. coli (EPEC) (Frankel et al. 1998; Fitzgerald and Musser 2001)
· EPEC > infantile diarrhea
· EHEC > "hamburger E. coli" fatalities
· Colonize intestinal mucosa
· Cause "attaching and effacing lesions" (A/E)

Locus of enterocyte effacement (LEE) (McDaniel and Kaper 1997; Frankel et al. 1998)
· Pathogenicity island present in both EPEC and EHEC
· Cloned from an EPEC strain and sufficient to confer A/E phenotype to E. coli K-12
· Encodes type III secretion system
· Translocates Tir protein to host cells
· Tir-intimin interactions lead to pedestal formation

Parallel evolution of virulence in pathogenic E. coli (Reid et al. 2000)
· EHEC and K-12 divergence 4.5 M years ago
· phylogenetic tree based on 7 housekeeping genes constructed
· LEE and multiple other virulence factors independently acquired
   o "The phylogenetic analysis suggests that gain and loss of mobile virulence elements has occurred several times, and in parallel in separate lineages of pathogenic E. coli"
   o "The parallel pattern of evolution suggests that there is a selective advantage favouring the build-up of specific combinations of virulence factors enabling the establishment and transmission of new virulent clones."

0157:H7 genome (Perna et al. 2001)
· 4.1 Mb backbone with 1.34 Mb of O-islands and 0.53 Mb of K-islands
· many O- and K-islands are in the same location in the backbone
· 9 large O-islands encode putative virulence functions
· most islands have GC content and 3rd codon preferences different from backbone
· many prophages or related elements
· many SNPs leave only 25% of the proteins identical

Variation among strains of O157 (Kudva et al. 2002)
· XbaI digestion followed by PFGE reveals heterogeneity among strains
· Heterogeneity due to insertions and deletion (indels) not XbaI site polymorphisms
· All indels were found to be in O-islands

Phages as a major source of O-island variation in 0157 (Ohnishi et al. 2001)
"Determination of the genome sequence of enterohemorrhagic Escherichia coli O157 Sakai and genomic comparison with the laboratory strain K-12 has revealed that the two strains share a highly conserved 4.1-Mb sequence and that each also contains a large amount of strain-specific sequence. The analysis also revealed the presence of a surprisingly large number of prophages in O157, most of which are lambda-like phages that resemble each other. Based on these results, we discuss how the E. coli strains have diverged from a common ancestral strain, and how bacteriophages contributed to this process. We also describe possible mechanisms by which O157 acquired many closely related phages, and raise the possibility that such bacteria might function as 'phage factories', releasing a variety of chimeric or mosaic phages into the environment."

Erwinia carotovora subsp. atroseptica genome (Bell et al. 2004)
· 33% of Eca genes lacking from sequenced enterobacterial animal pathogens
· several putative, horizontally acquired islands encoding interesting traits
· functional genomics discovery of the role of polyketide phytotoxin biosynthesis in virulence

References

Bell, K. S., Sebaihia, M., Pritchard, L., Holden, M. T., Hyman, L. J., Holeva, M. C., Thomson, N. R., Bentley, S. D., Churcher, L. J., Mungall, K., Atkin, R., Bason, N., Brooks, K., Chillingworth, T., Clark, K., Doggett, J., Fraser, A., Hance, Z., Hauser, H., Jagels, K., Moule, S., Norbertczak, H., Ormond, D., Price, C., Quail, M. A., Sanders, M., Walker, D., Whitehead, S., Salmond, G. P., Birch, P. R., Parkhill, J., and Toth, I. K. 2004. Genome sequence of the enterobacterial phytopathogen Erwinia carotovora subsp. atroseptica and characterization of virulence factors. Proc. Natl. Acad. Sci. U S A 101:11105-1110.

Fitzgerald, J. R., and Musser, J. M. 2001. Evolutionary genomics of pathogenic bacteria. Trends Microbiol. 9:547-553.
Frankel, G., Phillips, A. D., Rosenshine, I., Dougan, G., Kaper, J. B., and Knutton, S. 1998. Enteropathogenic and enterohaemorrhagic Escherichia coli: more subversive elements. Mol Microbiol 30:911-21.

Kudva, I. T., Evans, P. S., Perna, N. T., Barrett, T. J., Ausubel, F. M., Blattner, F. R., and Calderwood, S. B. 2002. Strains of Escherichia coli O157:H7 differ primarily by insertions or deletions, not single-nucleotide polymorphisms. J Bacteriol 184:1873-9.

McDaniel, T. K., and Kaper, J. B. 1997. A cloned pathogenicity island from enteropathogenic Escherichia coli confers the attaching and effacing phenotype on E. coli K-12. Mol. Microbiol. 23:399-407.

Ohnishi, M., Kurokawa, K., and Hayashi, T. 2001. Diversification of Escherichia coli genomes: are bacteriophages the major contributors? Trends Microbiol 9:481-5.

Perna, N. T., Plunkett, G., 3rd, Burland, V., Mau, B., Glasner, J. D., Rose, D. J., Mayhew, G. F., Evans, P. S., Gregor, J., Kirkpatrick, H. A., Posfai, G., Hackett, J., Klink, S., Boutin, A., Shao, Y., Miller, L., Grotbeck, E. J., Davis, N. W., Lim, A., Dimalanta, E. T., Potamousis, K. D., Apodaca, J., Anantharaman, T. S., Lin, J., Yen, G., Schwartz, D. C., Welch, R. A., and Blattner, F. R. 2001. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 409:529-533.

Reid, S. D., Herbelin, C. J., Bumbaugh, A. C., Selander, R. K., and Whittam, T. S. 2000. Parallel evolution of virulence in pathogenic Escherichia coli. Nature 406:64-7.

Slide 1

Return to top

Slide 2

Return to top

Slide 3

Return to top

Slide 4

Return to top

Slide 5

Return to top

Slide 6

Return to top

Slide 7

Return to top