Recurrent urinary tract infections in women despite antibiotic treatments: Novel tools uncovering microbial-host dynamics

Urinary tract infections (UTIs), primarily caused by uropathogenic Escherichia coli (UPEC), present a substantial global health challenge.

The increasing antibiotic resistance in UPEC highlights the pressing need for better insights into the factors behind recurrent UTIs (rUTIs) in healthy individuals.

Our aim is to create a detailed, comprehensive map of the host, pathogen and other microbiota factors that lead to rUTI.

To understand how UPEC transitions from gastro-intestinal (GIT) commensal bacteria to uropathogens, we will use innovative high-resolution approaches to study: Aim 1) the dynamics of the composition and transcriptional profiles of all microbiota, Aim 2) E. coli-strains on nucleotide level and identify strains prone to develop antibiotic resistance and Aim 3) relevant contributors to immune pathways that modulate the microbiota and UPEC along the gut-bladder axis prior to, during, and after UTI (the rUTI cycle).

Data from healthy timepoints will be compared to subsequent specimens derived from the GIT, vagina, and periurethra over the rUTI cycle.

This will be the first study to explore both the host and the bacterial processes that account for the changes in biogeography of the UPEC route to causing UTI, and how these dynamics affect rUTI incidence and outcome.

This will provide novel prevention and therapeutic strategies for rUTI, reduce the development of antibiotic drug resistant uropathogens and identify strains at risk for developing multi-resistance.