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

Sabine Kienesberger, Amar Cosic, Maksym Kitsera, Sandra Raffl, Marlene Hiesinger, Eva Leitner, Bettina Halwachs, Gregor Gorkiewicz, Ronald A Glabonjat, Georg Raber, Christian Lembacher-Fadum, Rolf Breinbauer, Stefan Schild, Ellen L Zechner*

*Korrespondierende/r Autor/-in für diese Arbeit

Publikation: Beitrag in einer FachzeitschriftArtikelBegutachtung

Abstract

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

Originalspracheenglisch
Seiten (von - bis)1834-1848
FachzeitschriftNature Microbiology
Jahrgang7
Ausgabenummer11
DOIs
PublikationsstatusVeröffentlicht - Nov. 2022

ASJC Scopus subject areas

  • Angewandte Mikrobiologie und Biotechnologie
  • Mikrobiologie (medizinisch)
  • Genetik
  • Zellbiologie
  • Mikrobiologie
  • Immunologie

Fields of Expertise

  • Human- & Biotechnology

Kooperationen

  • BioTechMed-Graz

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