Uropathogenic E. coli induces DNA damage in the bladder

Author summary Colibactin is a bacterial genotoxin suspected of being involved in cancer. So far, the focus has been on colorectal cancer following asymptomatic intestinal carriage of genotoxic Escherichia coli. Here, we show for the first time that this genotoxin is produced in humans, by detecting it in the urine of patients suffering from urinary tract infections. We subsequently show in a rodent UTI model the genotoxic activity of colibactin in the bladder, including in regenerative cells. These results raise the hypothesis of a role of UTI in bladder cancer, which could be an interesting perspective for future investigation. 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.