title: Citrobacter rodentium virulence in mice associates with bacterial load and the type III effector NleE.
abstract: Severe disease caused by Shiga toxin-producing Escherichia coli (STEC) has been associated with a pathogenicity island, O-Island 122, which encodes the type III secretion system-effector NleE. Here we show that full virulence of the related attaching and effacing mouse pathogen Citrobacter rodentium requires NleE. Relative to wild-type bacteria, nleE-mutant C. rodentium are attenuated for colonisation in mice in both single and mixed infections. Examination of the ability of nleE-mutant bacteria to induce pathologic change in vivo revealed that nleE-mutant bacteria induce significantly less pathologic change than wild-type bacteria in susceptible mice. Consistent with these results, mice infected with nleE-mutant bacteria exhibit delayed mortality. These results suggested that pathologic change during attaching and effacing pathogen infection may associate with the degree of pathogen colonisation. Using mutants of 23 type III secretion genes, including the type III effectors nleC, nleD, nleE and nleF, the association of pathologic change with the ability of these mutants to colonise mice was examined. The induction of in vivo disease correlates strongly with the degree of colonisation, suggesting that the colonisation advantage type III secretion genes afford the bacteria, contribute to, and are required for, full virulence.
authors.affiliation: Michael Smith Laboratories, The University of British Columbia, #301 2185 East Mall, Vancouver, BC V6T 1Z4, Canada. wickham@wehi.edu.au
authors.forename: Mark E
authors.initials: ME
authors.lastname: Wickham
authors.forename: Claudia
authors.initials: C
authors.lastname: Lupp
authors.forename: Alejandra
authors.initials: A
authors.lastname: Vázquez
authors.forename: Mariola
authors.initials: M
authors.lastname: Mascarenhas
authors.forename: Bryan
authors.initials: B
authors.lastname: Coburn
authors.forename: Brian K
authors.initials: BK
authors.lastname: Coombes
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Karmali
authors.forename: José L
authors.initials: JL
authors.lastname: Puente
authors.forename: Wanyin
authors.initials: W
authors.lastname: Deng
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D044082:Citrobacter rodentium / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D003106:Colon / Q000382:microbiology / Q000473:pathology; D017124:Conserved Sequence; D004756:Enterobacteriaceae Infections / Q000382:microbiology / Q000473:pathology; D044404:Genomic Islands; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D014774:Virulence; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors