Clostridium difficile toxin B is an inflammatory enterotoxin in human intestine.

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.

• Authors: Tor C Savidge, Wei-Hua Pan, Paul Newman, Michael O'brien, Pauline M Anton, Charalabos Pothoulakis
• Journal: Gastroenterology (Gastroenterology) Vol. 125 Issue 2 Pg. 413-20 (Aug 2003) ISSN: 0016-5085 [Print] United States
• PMID: 12891543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

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