Effects of purified Clostridium difficile toxin A on rabbit distal colon

Gastroenterology. 1995 Aug;109(2):348-54. doi: 10.1016/0016-5085(95)90320-8.

Abstract

Background & aims: Antibiotic-associated pseudomembranous colitis in humans is caused by proliferation of Clostridium difficile, which elaborates an enterotoxin toxin A that causes epithelial damage and altered motility in rabbit small intestine. The aim of this study was to assess the effects of toxin A on rabbit distal colonic motility and to relate this to histological damage and inflammatory mediator production.

Methods: Two hundred micrograms per milliliter of toxin A was placed in a distal colonic loop in anesthetized rabbits, and myoelectric activity was recorded for the following 7 hours. The colon was histologically evaluated and assayed for eicosanoid production. The effects of toxin A on longitudinal and circular muscle were also assessed in vitro.

Results: Beginning 1 hour after instillation, toxin A caused a significant increase in the number of spike bursts without altering slow wave frequency; this was associated with an increase in mucosal neutrophils and increased production of prostaglandin E2 and leukotrienes B4 and C4/D4/E4. Seven hours after administration of toxin A, mediator levels and myoelectric activity remained increased but significant mucosal damage was now also present. Toxin A did not affect longitudinal or circular muscle in vitro.

Conclusions: C. difficile toxin A caused a significant neutrophil infiltration and an increased myoelectric activity before producing mucosal damage. The myoelectric effect may be indirect, resulting from the production of motility-altering arachidonic acid metabolites.

MeSH terms

  • Animals
  • Bacterial Toxins / isolation & purification
  • Bacterial Toxins / pharmacology*
  • Clostridium difficile*
  • Colitis / pathology
  • Colon / drug effects*
  • Colon / metabolism
  • Colon / pathology
  • Dinoprostone / metabolism
  • Electrophysiology
  • Enterotoxins / isolation & purification
  • Enterotoxins / pharmacology*
  • Gastrointestinal Motility / drug effects*
  • Humans
  • In Vitro Techniques
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Leukotrienes / metabolism
  • Male
  • Muscle Contraction / drug effects
  • Rabbits

Substances

  • Bacterial Toxins
  • Enterotoxins
  • Leukotrienes
  • tcdA protein, Clostridium difficile
  • Dinoprostone