Abstract
Shiga toxin (Stx)-producing Escherichia coli (STEC) colonizes the large intestine causing a spectrum of disorders, including watery diarrhea, bloody diarrhea (hemorrhagic colitis), and hemolytic-uremic syndrome. It is estimated that hemolytic-uremic syndrome is the most common cause of acute renal failure in infants in Argentina. Stx is a multimeric toxin composed of one A subunit and five B subunits. In this study we demonstrate that the Stx2 B subunit inhibits the water absorption (Jw) across the human and rat colonic mucosa without altering the electrical parameters measured as transepithelial potential difference and short circuit current. The time-course Jw inhibition by 400 ng/ml purified Stx2 B subunit was similar to that obtained using 12 ng/ml Stx2 holotoxin suggesting that both, A and B subunits of Stx2 contributed to inhibit the Jw. Moreover, non-hemorrhagic fluid accumulation was observed in rat colon loops after 16 h of treatment with 3 and 30 ng/ml Stx2 B subunit. These changes indicate that Stx2 B subunit induces fluid accumulation independently of A subunit activity by altering the usual balance of intestinal absorption and secretion toward net secretion. In conclusion, our results suggest that the Stx2 B subunit, which is non-toxic for Vero cells, may contribute to the watery diarrhea observed in STEC infection. Further studies will be necessary to determine whether the toxicity of Stx2 B subunit may have pathogenic consequences when it is used as a component in an acellular STEC vaccine or as a vector in cancer vaccines.
Highlights
Shiga toxin-producing Escherichia coli (STEC), an important and emergent pathogen with various serotypes including O157:H7, has been linked to a spectrum of disorders, including watery diarrhea, bloody diarrhea, and hemolytic-uremic syndrome (HUS) [1,2]
The purpose of the present investigation was to study the ability of the Shiga toxin type 2 (Stx2) B subunit to produce physiological and morphological changes in human and rat colon
The Stx2 B subunit inhibited water absorption across the human and rat colonic mucosa mounted on an Ussing chamber, while Stx2 showed highly significant water absorption inhibition concomitant with morphological damage in colonic surface cells including an inflammatory response
Summary
Shiga toxin-producing Escherichia coli (STEC), an important and emergent pathogen with various serotypes including O157:H7, has been linked to a spectrum of disorders, including watery diarrhea, bloody diarrhea (hemorrhagic colitis), and hemolytic-uremic syndrome (HUS) [1,2] The virulence of these strains is determined to a large extent by the production of Shiga toxin type 1 (Stx1) and/or Shiga toxin type 2 (Stx). If protein synthesis is completely inhibited, cell death eventually occurs, and Stx may cross the intestinal barrier to mediate the vascular complications of disease including hemorrhagic colitis and HUS. Such cellular destruction may occur either through the effects of the Stx on protein synthesis or as consequence of other pathological processes, such as apoptosis. The variation in disease in response to Stx could be a consequence of different pathways and mechanisms involved in its movement through the intestinal epithelial cell barrier
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