title: Signal transduction responses following adhesion of verocytotoxin-producing Escherichia coli.
abstract: Attaching and effacing adhesion to epithelial cells is a pathognomonic feature of infection by both enteropathogenic Escherichia coli (EPEC) and certain strains of verocytotoxin-producing E. coli (VTEC). EPEC adhesion to tissue culture epithelial cells results in activation of the phosphatidylinositol pathway, with elevated levels of inositol 1,4,5-triphosphate and cytosolic free calcium. In this report, we show that VTEC also activate this signal transduction pathway in infected epithelial cells. Specifically, increased levels of inositol 1,4,5-triphosphate and intracellular free calcium were observed in HEp-2 cells infected with VTEC of serotype O157:H7. VTEC of serotypes O157:H7 and O113:H21 also induced increases in intracellular calcium levels in the human intestinal crypt-like cell line T84, even with minimal or no attaching and effacing activity as monitored by transmission electron microscopy. In contrast to EPEC, VTEC failed to induce tyrosine phosphorylation of epithelial cell proteins in HEp-2 and T84 cells, as determined by indirect immunofluorescence microscopy. These findings suggest that signal transduction responses to VTEC, including elevated levels of inositol triphosphates and intracellular free calcium, are independent of formation of the attaching and effacing lesion. Our findings also show that VTEC pathogenesis may involve signal transduction pathways that are distinct from those induced by EPEC infection.
authors.affiliation: Division of Gastroenterology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Ismaili
authors.forename: D J
authors.initials: DJ
authors.lastname: Philpott
authors.forename: M T
authors.initials: MT
authors.lastname: Dytoc
authors.forename: P M
authors.initials: PM
authors.lastname: Sherman
mesh_terms: D001422:Bacterial Adhesion; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004768:Enterotoxins / Q000633:toxicity*; D004926:Escherichia coli / Q000472:pathogenicity*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D010766:Phosphorylation; D019000:Phosphotyrosine; D022622:Shiga Toxin 1; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D022622:Shiga Toxin 1; D019000:Phosphotyrosine; D014443:Tyrosine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium