Glucose alters the evolutionary response to gentamicin in uropathogenic .

Urinary tract infections (UTI) are a major health and economic concern. Uropathogenic (UPEC) are the leading cause of UTI, and antibiotic-resistant UPEC are increasingly common. The microenvironment of the urinary tract is metabolically distinct, and there is growing interest in understanding the extent to which metabolism may influence UPEC infection and response to antibiotics, and how this varies between individuals. Diabetes, characterized in part by glycosuria, is a known risk factor for UTI and is associated with more severe infections. The role that glucose plays in driving UPEC evolution remains unclear. Through experimental evolution with a single UPEC isolate, we identified mutations in the RNA polymerase sigma factor associated with long-term glucose exposure. We found that the presence of the antibiotic gentamicin resulted in mutations in genes including , which encodes a potassium ion uptake system previously linked to aminoglycoside resistance, and in the autotransporter . Strikingly, these mutations were not present in populations exposed to a combination of both glucose and gentamicin. This suggests that glucose may influence the survival of mutants in gentamicin, providing new avenues for understanding the evolution and treatment of UPEC-mediated UTI in high-risk individuals.