title: Divergent signal transduction responses to infection with attaching and effacing Escherichia coli.
abstract: Shiga toxin-producing Escherichia coli (STEC) O157:H7 is an attaching and effacing pathogen that causes hemorrhagic colitis and the hemolytic-uremic syndrome. Although this organism causes adhesion pedestals, the cellular signals responsible for the formation of these lesions have not been clearly defined. We have shown previously that STEC O157:H7 does not induce detectable tyrosine phosphorylation of host cell proteins upon binding to eukaryotic cells and is not internalized into nonphagocytic epithelial cells. In the present study, tyrosine-phosphorylated proteins were detected under adherent STEC O157:H7 when coincubated with the non-intimately adhering, intimin-deficient, enteropathogenic E. coli (EPEC) strain CVD206. The ability to be internalized into epithelial cells was also conferred on STEC O157:H7 when coincubated with CVD206 ([158 +/- 21] % of control). Neither the ability to rearrange phosphotyrosine proteins nor that to be internalized into epithelial cells was evident following coincubation with another STEC O157:H7 strain or with the nonsignaling espB mutant of EPEC. E. coli JM101(pMH34/pSSS1C), which overproduces surface-localized O157 intimin, also rearranged tyrosine-phosphorylated and cytoskeletal proteins when coincubated with CVD206. In contrast, JM101 (pMH34/pSSS1C) demonstrated rearrangement of cytoskeletal proteins, but not tyrosine-phosphorylated proteins, when coincubated with intimin-deficient STEC (strains CL8KO1 and CL15). These findings indicate that STEC O157:H7 forms adhesion pedestals by mechanisms that are distinct from those in attaching and effacing EPEC. Taken together, these findings point to diverging signal transduction responses to infection with attaching and effacing bacterial enteropathogens.
authors.affiliation: Research Institute, The Hospital for Sick Children, Department of Medical Genetics, University of Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Ismaili
authors.forename: E
authors.initials: E
authors.lastname: McWhirter
authors.forename: M Y
authors.initials: MY
authors.lastname: Handelsman
authors.forename: J L
authors.initials: JL
authors.lastname: Brunton
authors.forename: P M
authors.initials: PM
authors.lastname: Sherman
mesh_terms: D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis; D002352:Carrier Proteins; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003967:Diarrhea / Q000209:etiology*; D019453:Escherichia coli O157 / Q000472:pathogenicity*; D029968:Escherichia coli Proteins; D006801:Humans; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D029968:Escherichia coli Proteins; C073819:eaeA protein, E coli; D019000:Phosphotyrosine; D014443:Tyrosine