Bacterial Genetic Determinants of Non‐O157 STEC Outbreaks and Hemolytic‐Uremic Syndrome after Infection
1Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, and 2Laboratory for Foodborne Zoonoses, Population and Public Health Branch, Health Canada, Guelph, and 3McMaster University, Hamilton, Ontario, Canada; 4Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mexico
Although O157:H7 Shiga toxin–producing Escherichia coli (STEC) are the predominant cause of hemolytic‐uremic syndrome (HUS) in the world, non‐O157:H7 serotypes are a medically important cause of HUS that are underdetected by current diagnostic approaches. Because Shiga toxin is necessary but not sufficient to cause HUS, identifying the virulence determinants that predict severe disease after non‐O157 STEC infection is of paramount importance. Disease caused by O157:H7 STEC has been associated with a 26‐gene pathogenicity island known as O island (OI) 122. To assess the public‐health significance of this pathogenicity island, we examined the association between OI122 genes and outbreaks and HUS after non‐O157 STEC infection. We found that a subset of OI122 genes is independently associated with outbreaks and HUS after infection with non‐O157 STEC. The presence of multiple virulence genes in non‐O157 serotypes strengthened this association, which suggests that the additive effects of a variable repertoire of virulence genes contribute to disease severity. In vivo, Citrobacter rodentium mutants lacking outbreak‐ and HUS‐associated genes were deficient for virulence in mice; in particular, nleB mutant bacteria were unable to cause mortality in mice. The present study shows that virulence genes associated epidemiologically with outbreaks and HUS after non‐O157 STEC infection are pivotal to the initiation, progression, and outcome of in vivo disease.
Received 9 January 2006; accepted 22 March 2006; electronically published 11 August 2006.
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Potential conflicts of interest: none reported.
Financial support: Howard Hughes Medical Institute (study funding); Canadian Institutes of Health Research (study funding, including the Institute of Infection and Immunity Safe Food and Water Program, postdoctoral fellowships to M.E.W. and B.K.C., and Distinguished Investigator award to B.B.F.); Michael Smith Foundation for Health Research (postdoctoral fellowships to M.E.W., C.L., B.K.C., and N.F.B.); Honorary Killam Postdoctoral Fellowship (to M.E.W.); Canadian Association for Gastroenterology (fellowship to C.L.); Dirección General de Asuntos del Personal Académico, Consejo Nacional de Ciencia y Tecnología (grant to J.L.P.); Howard Hughes International Research Scholar award (to J.L.P. and B.B.F.); University of British Columbia Peter Wall Distinguished Professorship (to B.B.F.).
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Present affiliation: Nature Publishing Group, London, UK (C.L.).