# Glucose alters the evolutionary response to gentamicin in uropathogenic Escherichia coli

## TL;DR

Glucose exposure changes how uropathogenic E. coli evolves in response to the antibiotic gentamicin, which could affect UTI treatment in people with diabetes.

## Contribution

The study reveals that glucose alters UPEC's evolutionary response to gentamicin, uncovering new mutation patterns and treatment implications.

## Key findings

- Long-term glucose exposure leads to mutations in the rpoS gene in UPEC.
- Gentamicin exposure causes mutations in trkH and hyxB genes.
- Combining glucose and gentamicin prevents these mutations, suggesting glucose influences survival of gentamicin-resistant mutants.

## Abstract

Urinary tract infections (UTI) are a major health and economic concern. Uropathogenic Escherichia coli (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 rpoS associated with long-term glucose exposure. We found that the presence of the antibiotic gentamicin resulted in mutations in genes including trkH, which encodes a potassium ion uptake system previously linked to aminoglycoside resistance, and in the autotransporter hyxB. 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.