Uropathogenic E. coli induces DNA damage in the bladder

PLoS Pathog. 2021 Feb 25;17(2):e1009310. doi: 10.1371/journal.ppat.1009310. eCollection 2021 Feb.

Abstract

Urinary tract infections (UTIs) are among the most common outpatient infections, with a lifetime incidence of around 60% in women. We analysed urine samples from 223 patients with community-acquired UTIs and report the presence of the cleavage product released during the synthesis of colibactin, a bacterial genotoxin, in 55 of the samples examined. Uropathogenic Escherichia coli strains isolated from these patients, as well as the archetypal E. coli strain UTI89, were found to produce colibactin. In a murine model of UTI, the machinery producing colibactin was expressed during the early hours of the infection, when intracellular bacterial communities form. We observed extensive DNA damage both in umbrella and bladder progenitor cells. To the best of our knowledge this is the first report of colibactin production in UTIs in humans and its genotoxicity in bladder cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • DNA Damage*
  • Escherichia coli Infections / genetics
  • Escherichia coli Infections / microbiology
  • Escherichia coli Infections / pathology*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mutagens / metabolism
  • Peptides / metabolism*
  • Polyketides / metabolism*
  • Urinary Bladder / metabolism
  • Urinary Bladder / microbiology
  • Urinary Bladder / pathology*
  • Urinary Tract Infections / genetics
  • Urinary Tract Infections / microbiology
  • Urinary Tract Infections / pathology*
  • Uropathogenic Escherichia coli / isolation & purification*

Substances

  • Mutagens
  • Peptides
  • Polyketides
  • colibactin

Grants and funding

This work was supported by grants from the French National Agency for Research(ANR; https://anr.fr/) (UTI-TOUL ANR-17-CE35-0010 (EO) and LiBacPain ANR-18-CE14-0039 (NC)) and the French National Institute for Health and Medical Research(INSERM, https://www.inserm.fr/) (two-years grant "poste d’accueil INSERM 2018"(CVC)). The funders had no role in study design, data collection and analysis, decision topublish, or preparation of the manuscript.