Inhibition of water absorption and selective damage to human colonic mucosa induced by Shiga toxin-2 are enhanced by Escherichia coli O157:H7 infection

Int J Med Microbiol. 2015 May;305(3):348-54. doi: 10.1016/j.ijmm.2015.02.002. Epub 2015 Mar 5.

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.

Keywords: Diarrhea; Human colon; STEC infection; Shiga toxin-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Colon / drug effects
  • Colon / pathology*
  • Colon / physiopathology*
  • Escherichia coli O157 / pathogenicity*
  • Histocytochemistry
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology*
  • Intestinal Mucosa / physiopathology*
  • Models, Theoretical
  • Shiga Toxin 2 / toxicity*
  • Water / metabolism

Substances

  • Shiga Toxin 2
  • Water