Enterotoxin tilimycin from gut-resident Klebsiella promotes mutational evolution and antibiotic resistance in mice

• DOI: 10.1038/s41564-022-01260-3
• Publication Date: 2022-10-26T16:04:06Z
• Authors: Sabine Kienesberger; Amar Cosic; Maksym Kitsera; Sandra Raffl; Marlene Hiesinger; Eva Leitner; Bettina Halwachs; Gregor Gorkiewicz; Ronald A. Glabonjat; Georg Raber; Christian Lembach...; Rolf Breinbauer; Stefan Schild; Ellen L. Zechner
• Keywords: Klebsiella; Klebsiella oxytoca

Abstract Klebsiella spp. that secrete the DNA-alkylating enterotoxin tilimycin colonize human intestinal tract. Numbers of toxigenic bacteria increase during antibiotic use, and resulting accumulation in lumen damages epithelium via genetic instability apoptosis. Here we examine impact this genotoxin on gut ecosystem. 16S rRNA sequencing faecal samples from mice colonized with oxytoca strains mechanistic analyses show is a pro-mutagenic affecting multiple phyla. Transient synthesis murine antagonized niche competitors, reduced microbial richness altered taxonomic composition microbiota both following exposure. Moreover, secretion increased rates mutagenesis co-resident opportunistic pathogens such as pneumoniae Escherichia coli , shown by de novo acquisition resistance. We conclude bacterial mutagen, flares genotoxic have potential to drive emergence resistance, destabilize shape its evolutionary trajectory.