title: Inhibition of water absorption and selective damage to human colonic mucosa induced by Shiga toxin-2 are enhanced by Escherichia coli O157:H7 infection.
abstract: Shiga toxin-producing Escherichia coli (STEC) strains are responsible for a variety of clinical syndromes including bloody and non-bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Although multiple serotypes of STEC have been isolated from hemorrhagic colitis cases, E. coli O157:H7 is by far the most prevalent serotype associated with HUS. Shiga toxin is the major virulence factor of E. coli O157:H7 and is responsible for the more severe symptoms of the infection. However, the mechanisms involved in the pathogenesis of diarrhea mediated by Stx2 are not well known. In this study, we have determined the effects of E. coli O157:H7 strain 125/99 wild type (wt) on the human colonic mucosa mounted in an Ussing chamber. In response to 125/99wt, an inhibition of water absorption across human colonic mucosa was observed. Histological sections showed severe necrosis with detachment of the surface epithelium, mononuclear inflammatory infiltrate and loss of goblet cells after 1h of incubation with 125/99wt. These alterations were not observed with the isogenic mutant strain lacking stx2 or with the filter-sterilized culture supernatant from the 125/99wt strain. These results indicate that the cell damages in human colon are induced by Stx2, and that Stx2 production is increased by the interaction with bacterial cells. Identification of host cell-derived factors responsible for increasing Stx2 can lead to new strategies for modulating STEC infections.
authors: Laboratorio de Fisiopatogenia, Departamento de Fisiología, Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors: Adriana
authors: A
authors: Albanese
authors: Laboratorio de Fisiopatogenia, Departamento de Fisiología, Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors: Elizabeth
authors: E
authors: Gerhardt
authors: Servicio de Cirugía del Hospital Churruca-Visca, Departamento de Cirugía, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors: Hugo
authors: H
authors: García
authors: Instituto de Biotecnología, Instituto Nacional de Tecnología Agropecuaria (INTA-Castelar), Buenos Aires, Argentina.
authors: Natalia
authors: N
authors: Amigo
authors: Instituto de Biotecnología, Instituto Nacional de Tecnología Agropecuaria (INTA-Castelar), Buenos Aires, Argentina.
authors: Angel
authors: A
authors: Cataldi
authors: Laboratorio de Fisiopatogenia, Departamento de Fisiología, Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors: Elsa
authors: E
authors: Zotta
authors: Laboratorio de Fisiopatogenia, Departamento de Fisiología, Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. Electronic address: ibarra@fmed.uba.ar.
authors: Cristina
authors: C
authors: Ibarra
mesh_terms: D000328:Adult; D003106:Colon / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D019453:Escherichia coli O157 / Q000472:pathogenicity*; D006651:Histocytochemistry; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D008962:Models, Theoretical; D022641:Shiga Toxin 2 / Q000633:toxicity*; D014867:Water / Q000378:metabolism
chemical_list: D022641:Shiga Toxin 2; D014867:Water
keywords: Diarrhea; Human colon; STEC infection; Shiga toxin-2