Binary Toxin-Producing, Large Clostridial Toxin-Negative Clostridium Difficile Strains Are Enterotoxic but Do Not Cause Disease in Hamsters

J Infect Dis. 2006 Apr 15;193(8):1143-50. doi: 10.1086/501368. Epub 2006 Mar 6.

Abstract

Binary toxin CDT or its genes have been identified in some strains of Clostridium difficile that also produce the large clostridial toxins, toxins A and B (A+B+CDT+), including a newly recognized epidemic strain in the United States and Canada. To study the effects of binary toxin alone, we characterized 4 binary toxin CDT-positive only (A-B-CDT+) C. difficile strains. Unlike other clostridial binary toxins, binary toxin CDT required exogenous trypsin for activation. Supernatants from all A-B-CDT+ strains caused marked fluid accumulation in the rabbit ileal loop assay after concentration and trypsinization. In addition, the ileal loop response was neutralized by antisera raised against other binary toxin-producing clostridia. Challenge of clindamycin-treated hamsters with these strains resulted in colonization but not diarrhea or death. Binary toxin CDT may play an adjunctive role to toxins A and B in the pathogenesis of C. difficile-associated disease but by itself may not be sufficient to cause disease.

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / classification
  • Bacterial Proteins / metabolism*
  • Bacterial Toxins / biosynthesis
  • Bacterial Toxins / classification
  • Bacterial Toxins / metabolism*
  • Clindamycin / administration & dosage
  • Clostridium difficile / pathogenicity*
  • Clostridium difficile / physiology*
  • Cricetinae
  • Disease Models, Animal
  • Enterocolitis, Pseudomembranous / microbiology
  • Enterotoxins / biosynthesis
  • Enterotoxins / classification
  • Enterotoxins / metabolism*
  • Feces / microbiology
  • Ileum / pathology
  • Immune Sera / metabolism
  • Intestines / microbiology
  • Mesocricetus
  • Rabbits
  • Trypsin / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Bacterial Toxins
  • Enterotoxins
  • Immune Sera
  • enterotoxin, Clostridium
  • toxB protein, Clostridium difficile
  • Clindamycin
  • Trypsin