title: Novel effects of the prototype translocating Escherichia coli, strain C25 on intestinal epithelial structure and barrier function.
abstract: Intestinal bacteria play an etiologic role in triggering and perpetuating chronic inflammatory bowel disorders. However, the precise mechanisms whereby the gut microflora influences intestinal cell function remain undefined. Therefore, the effects of the non-pathogenic prototype translocating Escherichia coli, strain C25 on the barrier properties of human T84 and Madine-Darby canine kidney type 1 epithelial cells were examined. T-84 cells were also infected with commensal E. coil, strains F18 and HB101, and enterohaemorrhagic E. coli, serotype O157:H7. Strains F18 and HB101 had no effect on transepithelial electrical resistance (TER) of T84 monolayers. By contrast, epithelial cells infected with strain C25 displayed a time-dependent decrease in TER, preceded by an altered distribution of the cytoskeletal protein alpha-actinin, comparable to infection with E. coli O157:H7. E. coli C25 infection also led to activation of nuclear factor kappaB (NF-kappaB), interleukin-8 secretion and alterations in localization of claudin-1, but not zona occludens-1 or claudin-4, in T84 cells. There were adherent C25 bacteria on the intact apical surface of infected T84 cells, while mitochondria appeared swollen and vacuolated. These novel findings demonstrate the ability of a translocating commensal bacterium to adhere to and modulate intestinal epithelial barrier function and to induce morphological changes in a manner distinct from the known enteric pathogen, E. coli O157:H7.
authors.affiliation: Research Institute, Hospital for Sick Children, Department of Paediatrics and Laboratory Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Mehri
authors.initials: M
authors.lastname: Zareie
authors.forename: Jason
authors.initials: J
authors.lastname: Riff
authors.forename: Kevin
authors.initials: K
authors.lastname: Donato
authors.forename: Derek M
authors.initials: DM
authors.lastname: McKay
authors.forename: Mary H
authors.initials: MH
authors.lastname: Perdue
authors.forename: Johan D
authors.initials: JD
authors.lastname: Soderholm
authors.forename: Mohamed
authors.initials: M
authors.lastname: Karmali
authors.forename: Mitchell B
authors.initials: MB
authors.lastname: Cohen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hawkins
authors.forename: Philip M
authors.initials: PM
authors.lastname: Sherman
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D002460:Cell Line; D062445:Claudin-1; D004926:Escherichia coli / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism
chemical_list: C568108:CLDN1 protein, human; D062445:Claudin-1; D016209:Interleukin-8; D008565:Membrane Proteins; D016328:NF-kappa B