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Enterotoxicity of a nonribosomal peptide causes antibiotic-associated colitis

Georg Schneditz1, Jana Rentner2, Sandro Roier1

  • 1Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria;

Proceedings of the National Academy of Sciences of the United States of America
|August 27, 2014
PubMed

Insights

The bacterium Klebsiella oxytoca produces a toxin, tilivalline, that causes antibiotic-associated hemorrhagic colitis (AAHC). This toxin disrupts gut barrier function and induces cell death, offering targets for colitis treatment.

Area of Science:

  • Microbiology
  • Gastroenterology
  • Toxicology

Background:

  • Antibiotic use can disrupt the gut microbiota.
  • Overgrowth of Klebsiella oxytoca is linked to antibiotic-associated hemorrhagic colitis (AAHC).

Purpose of the Study:

  • To identify the toxin produced by K. oxytoca responsible for AAHC.
  • To investigate the mechanism of tilivalline-induced colitis in vitro and in vivo.

Main Methods:

  • Isolation and identification of K. oxytoca toxin.
  • In vitro studies using cultured human cells.
  • Animal model of antibiotic-associated colitis.

Main Results:

  • The pyrrolobenzodiazepine tilivalline was identified as the causative toxin.
  • Tilivalline induced apoptosis and disrupted epithelial barrier function in vitro.
  • Tilivalline demonstrated causative action in the pathogenesis of colitis in an animal model.

Conclusions:

  • Pyrrolobenzodiazepines are present in the intestinal microbiota.
  • Tilivalline is a key factor in AAHC pathogenesis.
  • Tilivalline represents a potential diagnostic and therapeutic target for colitis.
Keywords:
bacteriacytotoxinenteric microbiota

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