It takes two to tango: Klebsiella oxytoca overgrowth and production of Tilivalline, a cytotoxin, are the key events causing Antibiotic-Associated Hemorrhagic Colitis

Background: Klebsiella oxytoca is a member of the enteric microflora of humans that typically behaves as a commensal. However, β-lactamase expression enables this bacterium to dominate the intestinal flora during antibiotic therapy and cause antibiotic-associated hemorrhagic colitis (AAHC). Here we define the structure and function of a cytotoxin secreted by K. oxytoca and its involvement in AAHC. Methods and Results: General and site-directed mutagenesis of a toxin-producing K. oxytoca strain, combined with an in vitro screen for epithelial cytotoxicity identified a cluster of non-ribosomal peptide synthesis ge…