Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schneditz, G; Rentner, J; Roier, S; Pletz, J; Herzog, KA; Bücker, R; Troeger, H; Schild, S; Weber, H; Breinbauer, R; Gorkiewicz, G; Högenauer, C; Zechner, EL.
Enterotoxicity of a nonribosomal peptide causes antibiotic-associated colitis.
Proc Natl Acad Sci U S A. 2014; 111(36):13181-13186
Doi: 10.1073/pnas.1403274111
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- Führende Autor*innen der Med Uni Graz
- Hoegenauer Christoph
- Co-Autor*innen der Med Uni Graz
- Gorkiewicz Gregor
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Actinobacteria - metabolism
- Animals -
- Anti-Bacterial Agents - adverse effects
- Apoptosis - drug effects
- Benzodiazepinones - toxicity
- Caspase 3 - metabolism
- Colitis - chemically induced Colitis - pathology
- Cytotoxins - toxicity
- Enterotoxins - toxicity
- Epithelial Cells - drug effects Epithelial Cells - microbiology Epithelial Cells - pathology
- Humans -
- Klebsiella oxytoca - genetics
- Mice, Inbred C57BL -
- Molecular Sequence Data -
- Multigene Family -
- Penicillins - pharmacology
- Peptide Synthases - metabolism
- Peptides - toxicity
- Ribosomes -
- Find related publications in this database (Keywords)
- bacteria
- enteric microbiota
- cytotoxin