title: Bacterial genetic determinants of non-O157 STEC outbreaks and hemolytic-uremic syndrome after infection.
abstract: 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.
authors.affiliation: Michael Smith Laboratories, University of British Columbia, Vancouver BC, Canada.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Wickham
authors.forename: Claudia
authors.initials: C
authors.lastname: Lupp
authors.forename: Mariola
authors.initials: M
authors.lastname: Mascarenhas
authors.forename: Alejandra
authors.initials: A
authors.lastname: Vazquez
authors.forename: Brian K
authors.initials: BK
authors.lastname: Coombes
authors.forename: Nat F
authors.initials: NF
authors.lastname: Brown
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Coburn
authors.forename: Wanyin
authors.initials: W
authors.lastname: Deng
authors.forename: Jose L
authors.initials: JL
authors.lastname: Puente
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Karmali
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
mesh_terms: D000818:Animals; D044082:Citrobacter rodentium / Q000235:genetics / Q000472:pathogenicity; D003106:Colon / Q000382:microbiology; D017931:DNA Primers; D004195:Disease Models, Animal; D004196:Disease Outbreaks; D004926:Escherichia coli / Q000235:genetics* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000453:epidemiology / Q000382:microbiology*; D044404:Genomic Islands / Q000235:genetics* / Q000502:physiology; D006463:Hemolytic-Uremic Syndrome / Q000453:epidemiology / Q000382:microbiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D015995:Prevalence; D022603:Shiga Toxins / Q000096:biosynthesis; D016019:Survival Analysis; D013997:Time Factors; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics
chemical_list: D017931:DNA Primers; D022603:Shiga Toxins; D037521:Virulence Factors