Clostridium Difficile Toxin B Is an Inflammatory Enterotoxin in Human Intestine

Gastroenterology. 2003 Aug;125(2):413-20. doi: 10.1016/s0016-5085(03)00902-8.

Abstract

Background & aims: Clostridium difficile causes antibiotic-associated diarrhea and pseudomembranous colitis, diseases afflicting millions of people each year. Although C. difficile releases 2 structurally similar exotoxins, toxin A and toxin B, animal experiments suggest that only toxin A mediates diarrhea and enterocolitis. However, toxin A-negative/toxin B-positive strains of C. difficile recently were isolated from patients with antibiotic-associated diarrhea and colitis, indicating that toxin B also may be pathogenic in humans.

Methods: Here we used subcutaneously transplanted human intestinal xenografts in immunodeficient mice to generate a chimeric animal model for C. difficile toxin-induced pathology of human intestine.

Results: We found that intraluminal toxin B, like equivalent concentrations of toxin A, induced intestinal epithelial cell damage, increased mucosal permeability, stimulated interleukin (IL)-8 synthesis, and caused an acute inflammatory response characterized by neutrophil recruitment and tissue damage. Laser capture microdissection and real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) showed that intestinal epithelial cell-specific IL-8 gene expression also was increased significantly after luminal exposure to C. difficile toxins in vivo.

Conclusions: We conclude that C. difficile toxin B, like toxin A, is a potent inflammatory enterotoxin for human intestine. Future therapeutic or vaccine strategies for C. difficile infection therefore need to target both toxins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Animals
  • Bacterial Proteins*
  • Bacterial Toxins / toxicity*
  • Clostridium difficile / pathogenicity*
  • Enterotoxins / toxicity*
  • Humans
  • Interleukin-8 / genetics
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects
  • Mice
  • Mice, SCID
  • Permeability
  • Phenotype
  • RNA, Messenger / analysis
  • Transplantation, Heterologous

Substances

  • Bacterial Proteins
  • Bacterial Toxins
  • Enterotoxins
  • Interleukin-8
  • RNA, Messenger
  • toxB protein, Clostridium difficile