title: Enterohaemorrhagic Escherichia coli O157:H7 Shiga-like toxin 1 is required for full pathogenicity and activation of the p38 mitogen-activated protein kinase pathway in Caenorhabditis elegans.
abstract: Enterohaemorrhagic Escherichia coli (EHEC) causes life-threatening infections in humans as a consequence of the production of Shiga-like toxins. Lack of a good animal model system currently hinders in vivo study of EHEC virulence by systematic genetic methods. Here we applied the genetically tractable animal, Caenorhabditis elegans, as a surrogate host to study the virulence of EHEC as well as the host immunity to this human pathogen. Our results show that E. coli O157:H7, a serotype of EHEC, infects and kills C. elegans. Bacterial colonization and induction of the characteristic attaching and effacing (A/E) lesions in the intact intestinal epithelium of C. elegans by E. coli O157:H7 were concomitantly demonstrated in vivo. Genetic analysis indicated that the Shiga-like toxin 1 (Stx1) of E. coli O157:H7 is a virulence factor in C. elegans and is required for full toxicity. Moreover, the C. elegans p38 mitogen-activated protein kinase (MAPK) pathway, an evolutionarily conserved innate immune and stress response signalling pathway, is activated in the regulation of host susceptibility to EHEC infection in a Stx1-dependent manner. Our results validate the EHEC-C. elegans interaction as suitable for future comprehensive genetic screens for both novel bacterial and host factors involved in the pathogenesis of EHEC infection.
authors.affiliation: Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: T-C
authors.initials: TC
authors.lastname: Chou
authors.forename: H-C
authors.initials: HC
authors.lastname: Chiu
authors.forename: C-J
authors.initials: CJ
authors.lastname: Kuo
authors.forename: C-M
authors.initials: CM
authors.lastname: Wu
authors.forename: W-J
authors.initials: WJ
authors.lastname: Syu
authors.forename: W-T
authors.initials: WT
authors.lastname: Chiu
authors.forename: C-S
authors.initials: CS
authors.lastname: Chen
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology*; D004927:Escherichia coli Infections; D019453:Escherichia coli O157 / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D023421:Models, Animal; D022622:Shiga Toxin 1 / Q000378:metabolism*; D016019:Survival Analysis; D037521:Virulence Factors / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis*
chemical_list: D022622:Shiga Toxin 1; D037521:Virulence Factors; D048051:p38 Mitogen-Activated Protein Kinases