Evidence that Clostridium perfringens enterotoxin-induced intestinal damage and enterotoxemic death in mice can occur independently of intestinal caspase-3 activation

John C. Freedman, Mauricio A. Navarro, Eleonora Morrell, Juliann Beingesser, Archana Shrestha, Bruce A. McClane, Francisco A Uzal

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Clostridium perfringens enterotoxin (CPE) is responsible for the gastrointestinal symptoms of C. perfringens type A food poisoning and some cases of nonfoodborne gastrointestinal diseases, such as antibiotic-associated diarrhea. In the presence of certain predisposing medical conditions, this toxin can also be absorbed from the intestines to cause enterotoxemic death. CPE action in vivo involves intestinal damage, which begins at the villus tips. The cause of this CPE-induced intestinal damage is unknown, but CPE can induce caspase-3-mediated apoptosis in cultured enterocyte-like Caco-2 cells. Therefore, the current study evaluated whether CPE activates caspase-3 in the intestines and, if so, whether this effect is required for the development of intestinal tissue damage or enterotoxemic lethality. Using a mouse ligated small intestinal loop model, CPE was shown to cause intestinal caspase-3 activation in a dose- and time-dependent manner. Most of this caspase-3 activation occurred in epithelial cells shed from villus tips. However, CPE-induced caspase-3 activation occurred after the onset of tissue damage. Furthermore, inhibition of intestinal caspase-3 activity did not affect the onset of intestinal tissue damage. Similarly, inhibition of intestinal caspase-3 activity did not reduce CPE-induced enterotoxemic lethality in these mice. Collectively, these results demonstrate that caspase-3 activation occurs in the CPE-treated intestine but that this effect is not necessary for the development of CPE-induced intestinal tissue damage or enterotoxemic lethality.

Original languageEnglish (US)
Article numbere00931-17
JournalInfection and Immunity
Volume86
Issue number7
DOIs
StatePublished - Jul 1 2018

Keywords

  • Caspase-3
  • Clostridium perfringens
  • Enterotoxemia
  • Enterotoxin
  • Intestinal damage

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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