Enterotoxicity of a nonribosomal peptide causes antibiotic-associated colitis

Georg Schneditz, Jana Rentner, Sandro Roier, Jakob Pletz, Kathrin A.T. Herzog, Roland Bücker, Hanno Troeger, Stefan Schild, Hansjörg Weber, Rolf Breinbauer, Gregor Gorkiewicz, Christoph Högenauer*, Ellen L. Zechner

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Antibiotic therapy disrupts the human intestinal microbiota. In some patients rapid overgrowth of the enteric bacterium Klebsiella oxytoca results in antibiotic-associated hemorrhagic colitis (AAHC). We isolated and identified a toxin produced by K. oxytoca as the pyrrolobenzodiazepine tilivalline and demonstrated its causative action in the pathogenesis of colitis in an animal model. Tilivalline induced apoptosis in cultured human cells in vitro and disrupted epithelial barrier function, consistent with the mucosal damage associated with colitis observed in human AAHC and the corresponding animal model. Our findings reveal the presence of pyrrolobenzodiazepines in the intestinal microbiota and provide a mechanism for colitis caused by a resident pathobiont. The data link pyrrolobenzodiazepines to human disease and identify tilivalline as a target for diagnosis and neutralizing strategies in prevention and treatment of colitis.

Original languageEnglish
Pages (from-to)13181-13186
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number36
Publication statusPublished - 2014


  • Bacteria
  • Cytotoxin
  • Enteric microbiota

ASJC Scopus subject areas

  • General

Fields of Expertise

  • Human- & Biotechnology

Treatment code (Nähere Zuordnung)

  • Basic - Fundamental (Grundlagenforschung)
  • My Favorites
  • Experimental


Dive into the research topics of 'Enterotoxicity of a nonribosomal peptide causes antibiotic-associated colitis'. Together they form a unique fingerprint.

Cite this