1887

Abstract

Intimin is an outer-membrane adhesin that is essential for colonization of the host gastrointestinal tract by attaching and effacing pathogens including enteropathogenic (EPEC), enterohaemorrhagic (EHEC) and (CR). The N-terminus of intimin from the different strains is highly conserved while the C-terminus, which harnesses the active receptor-binding site, shows sequence and antigenic polymorphism. This diversity was used to define a number of distinct intimin types, the most common of which are , and . Intimin binds the type III secretion system effector protein Tir. However, a large body of evidence suggests that intimin also binds a host-cell-encoded receptor(s) (Hir), and interaction of different intimin types with Hir contributes to tissue and host specificity. The aims of this study were to compare the activity of the major intimin types (, and ) and , using the CR mouse model and organ culture (IVOC), and to determine their exchangeability. The results confirm that intimin is not functional in the CR mouse model. In the pig, intimin can substitute for EPEC intimin but when placed in an EHEC O157 : H7 background it does not produce an intimin -like tropism, although some adhesion to the small and large intestine was observed. In contrast, in human IVOC, intimin in an EHEC background produces small intestinal colonization in a similar manner to intimin .

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.2006/003467-0
2007-04-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/micro/153/4/959.html?itemId=/content/journal/micro/10.1099/mic.0.2006/003467-0&mimeType=html&fmt=ahah

References

  1. Adu-Bobie J., Frankel G., Bain C., Goncaleves A. G., Trabulsi L. R., Douce G., Knutton S., Dougan G. 1998; Detection of intimin α , β , γ , and δ , four intimin derivatives expressed by attaching and effacing microbial pathogens. J Clin Microbiol 36:662–668
    [Google Scholar]
  2. Brooks J. T., Sowers E. G., Wells J. G., Greene K. D., Griffin P. M., Hoekstra R. M., Strockbine N. A. 2005; Non-O157 shiga toxin-producing Escherichia coli infections in the United States, 1983–2002. J Infect Dis 192:1422–1429 [CrossRef]
    [Google Scholar]
  3. Chen H. D., Frankel G. 2005; Enteropathogenic Escherichia coli : unravelling pathogenesis. FEMS Microbiol Rev 29:83–98 [CrossRef]
    [Google Scholar]
  4. Deng W., Vallance B. A., Li Y., Puente J. L., Finlay B. B. 2003; Citrobacter rodentium translocated intimin receptor (Tir) is an essential virulence factor needed for actin condensation, intestinal colonization and colonic hyperplasia in mice. Mol Microbiol 48:95–115 [CrossRef]
    [Google Scholar]
  5. Donnenberg M. S., Kaper J. B. 1991; Construction of an eae deletion mutant of enteropathogenic Escherichia coli by using a positive-selection suicide vector. Infect Immun 59:4310–4317
    [Google Scholar]
  6. Fitzhenry R. J., Pickard D. J., Hartland E. L., Reece S., Dougan G., Phillips A. D., Frankel G. 2002a; Intimin type influences the site of human intestinal mucosal colonisation by enterohaemorrhagic Escherichia coli O157 : H7. Gut 50:180–185 [CrossRef]
    [Google Scholar]
  7. Fitzhenry R. J., Reece S., Trabulsi L. R., Heuschkel R., Murch S., Thomson M., Frankel G., Phillips A. D. 2002b; Tissue tropism of enteropathogenic Escherichia coli strains belonging to the O55 serogroup. Infect Immun 70:4362–4368 [CrossRef]
    [Google Scholar]
  8. Frankel G., Candy D. C., Everest P., Dougan G. 1994; Characterization of the C-terminal domains of intimin-like proteins of enteropathogenic and enterohemorrhagic Escherichia coli , Citrobacter freundii , and Hafnia alvei . Infect Immun 62:1835–1842
    [Google Scholar]
  9. Frankel G., Candy D. C., Fabiani E., Adu-Bobie J., Gil S., Novakova M., Phillips A. D., Dougan G. 1995; Molecular characterization of a carboxy-terminal eukaryotic-cell-binding domain of intimin from enteropathogenic Escherichia coli . Infect Immun 63:4323–4328
    [Google Scholar]
  10. Frankel G., Lider O., Hershkoviz R., Mould A. P., Kachalsky S. G., Candy D. C. A., Cahalon L., Humphries M. J., Dougan G. 1996a; The cell-binding domain of intimin from enteropathogenic Escherichia coli binds to beta1 integrins. J Biol Chem 271:20359–20364 [CrossRef]
    [Google Scholar]
  11. Frankel G., Phillips A. D., Novakova M., Field H., Candy D. C., Schauer D. B., Douce G., Dougan G. 1996b; Intimin from enteropathogenic Escherichia coli restores murine virulence to a Citrobacter rodentium eaeA mutant: induction of an immunoglobulin A response to intimin and EspB. Infect Immun 64:5315–5325
    [Google Scholar]
  12. Frankel G., Philips A. D., Novakova M., Batchelor M., Hicks S., Dougan G. 1998; Generation of Escherichia coli intimin-derivatives with differing biological activities using site-directed mutagenesis of the intimin C-terminus domain. Mol Microbiol 29:559–570 [CrossRef]
    [Google Scholar]
  13. Garmendia J., Frankel G., Crepin V. F. 2005; Enteropathogenic and enterohaemorrhagic E. coli infections: translocation, translocation, translocation. Infect Immun 73:2586–2594 [CrossRef]
    [Google Scholar]
  14. Girard F., Batisson I., Frankel G., Harel J., Fairbrother J. M. 2005; Interaction of enteropathogenic and Shiga toxin-producing Escherichia coli and porcine intestinal mucosa: role of intimin and Tir in adherence. Infect Immun 73:6005–6016 [CrossRef]
    [Google Scholar]
  15. Hartland E. L., Huter V., Higgins L. M., Goncalves N. S., Dougan G., Phillips A. D., MacDonald T. T., Frankel G. 2000; Expression of intimin gamma from enterohemorrhagic Escherichia coli in Citrobacter rodentium . Infect Immun 68:4637–4646 [CrossRef]
    [Google Scholar]
  16. Hicks S., Frankel G., Kaper J. B., Dougan G., Phillips A. D. 1998; Role of intimin and bundle foming pili in enteropathgenic Escherichia coli adhesion to paediatric intestine in vitro. Infect Immun 66:1570–1578
    [Google Scholar]
  17. Jarvis K. G., Giron J. A., Jerse A. E., McDaniel T. K., Donnenberg M. S., Kaper J. B. 1995; Enteropathogenic Escherichia coli contains a putative type III secretion system necessary for the export of proteins involved in attaching and effacing lesion formation. Proc Natl Acad Sci U S A 92:7996–8000 [CrossRef]
    [Google Scholar]
  18. Jerse A. E., Yu J., Tall B. D., Kaper J. B. 1990; A genetic locus of enteropathogenic Escherichia coli necessary for the production of attaching and effacing lesions on tissue culture cells. Proc Natl Acad Sci U S A 87:7839–7843 [CrossRef]
    [Google Scholar]
  19. Kelly G., Prasannan S., Daniell S., Flemming K., Frankel G., Dougan G., Connerton I., Matthews S. 1999; Intimin from enteropathogenic E. coli belongs to a new family of bacterial adhesion molecules containing C-type lectin- and tandem immunoglobulin-like domains. Nature Structural Biol 6:313–318 [CrossRef]
    [Google Scholar]
  20. Kenny B., DeVinney R., Stein M., Reinscheid D. J., Frey E. A., Finlay B. B. 1997; Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells. Cell 91:511–520 [CrossRef]
    [Google Scholar]
  21. Luo Y., Frey E. A., Pfuetzner R. A., Creagh A. L., Knoechel D. G., Haynes C. A., Finlay B. B., Strynadka N. C. 2000; Crystal structure of enteropathogenic Escherichia coli intimin-receptor complex. Nature 405:1073–1077 [CrossRef]
    [Google Scholar]
  22. McDaniel T. K., Jarvis K. G., Donnenberg M. S., Kaper J. B. 1995; A genetic locus of enterocyte effacement conserved among diverse enterobacterial pathogens. Proc Natl Acad Sci U S A 92:1664–1668 [CrossRef]
    [Google Scholar]
  23. Mead P. S., Slutsker L., Griffin P. M., Tauxe R. V. 1999; Food-related illness and death in the United States reply to Dr. Hedberg. Emerg Infect Dis 5:841–842 [CrossRef]
    [Google Scholar]
  24. Mundy R., MacDonald T. T., Dougan G., Frankel G., Wiles S. 2005; Citrobacter rodentium of mice and man. Cell Microbiol 7:1697–1706 [CrossRef]
    [Google Scholar]
  25. Nataro J. P., Kaper J. B. 1998; Diarrheagenic Escherichia coli . Clin Microbiol Rev 11:142–201
    [Google Scholar]
  26. Phillips A. D., Frankel G. 2000; Intimin-mediated tissue specificity in enteropathogenic Escherichia coli interaction with human intestinal organ cultures. J Infect Dis 181:1496–1500 [CrossRef]
    [Google Scholar]
  27. Schauer D. B., Falkow S. 1993; The eae gene of Citrobacter freundii biotype 4280 is necessary for colonization in transmissible murine colonic hyperplasia. Infect Immun 61:4654–4661
    [Google Scholar]
  28. Sinclair J. F., O'Brien A. D. 2004; Intimin types alpha, beta, and gamma bind to nucleolin with equivalent affinity but lower avidity than to the translocated intimin receptor. J Biol Chem 279:33751–33758 [CrossRef]
    [Google Scholar]
  29. Thorpe C. M. 2004; Shiga toxin-producing Escherichia coli infection. Clin Infect Dis 38:1298–1303 [CrossRef]
    [Google Scholar]
  30. Tzipori S., Gunzer F., Donnenberg M. S., Kaper J. B., Donohue-Rolfe A., de Montigny L. 1995; The role of the eaeA gene in diarrhea and neurological complications in a gnotobiotic piglet model of enterohemorrhagic Escherichia coli infection. Infect Immun 63:3621–3627
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.2006/003467-0
Loading
/content/journal/micro/10.1099/mic.0.2006/003467-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error