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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Gorkiewicz, Gregor Troeger, Hanno Roier, Sandro Zechner, Ellen L. Herzog, Kathrin A. T. Breinbauer, Rolf Schneditz, Georg Bücker, Roland Weber, Hansjörg Rentner, Jana Pletz, Jakob Högenauer, Christoph Schild, Stefan |
| Description | Author Affiliation: Schneditz G ( Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria); Rentner J ( Institute of Organic Chemistry, Graz University of Technology, 8010 Graz, Austria); Roier S ( Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria); Pletz J ( Institute of Organic Chemistry, Graz University of Technology, 8010 Graz, Austria); Herzog KA ( Division of Gastroenterology and Hepatology, Department of Internal Medicine and.); Bücker R ( Department of Gastroenterology, Infectiology and Rheumatology, Charité - Campus Benjamin Franklin, 10117 Berlin, Germany.); Troeger H ( Department of Gastroenterology, Infectiology and Rheumatology, Charité - Campus Benjamin Franklin, 10117 Berlin, Germany.); Schild S ( Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria); Weber H ( Institute of Organic Chemistry, Graz University of Technology, 8010 Graz, Austria); Breinbauer R ( Institute of Organic Chemistry, Graz University of Technology, 8010 Graz, Austria); Gorkiewicz G ( Institute of Pathology, Medical University of Graz, 8036 Graz, Austria); Högenauer C ( Division of Gastroenterology and Hepatology, Department of Internal Medicine and christoph.hoegenauer@medunigraz.at ellen.zechner@uni-graz.at.); Zechner EL ( Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria); |
| 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 36 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Anti-Bacterial Agents Adverse Effects Benzodiazepinones Toxicity Colitis Chemically Induced Enterotoxins Peptides Actinobacteria Metabolism Animals Apoptosis Drug Effects Caspase 3 Pathology Cytotoxins Epithelial Cells Microbiology Klebsiella Oxytoca Genetics Mice, Inbred C57BL Molecular Sequence Data Multigene Family Penicillins Pharmacology Peptide Synthases Ribosomes Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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