# Roles of vaginal bacteria in bladder exfoliation and recurrent UTI

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2020 · $235,938

## Abstract

PROJECT SUMMARY
Urinary tract infection (UTI) is a costly clinical problem that affects millions of women worldwide. Clinical studies
implicate bacterial vaginosis (BV)—an imbalance of the vaginal microbiota—in enhancing susceptibility to
different UTI outcomes, but experimental models have not explained the underlying mechanisms. One of the
strongest risk factors for UTI is frequent and/or recent sexual activity. It is likely that vaginal bacteria are
commonly introduced into the bladder in sexually active women. Indeed, several vaginal bacteria—most
frequently Gardnerella vaginalis (G.v.) and Lactobacillus crispatus (L.c.)— have been isolated from urine
collected directly from the bladder by needle aspiration. G.v. is found at high levels during BV. Although culture
conditions are not often poised to detect it, its presence in urine has been associated with a history of recurrent
UTI (rUTI). L.c. is widely regarded as a “healthy” vaginal bacterium and is most often isolated from healthy
women without lower urinary tract symptoms. Our new mouse model shows that when G.v. gains access to the
urinary tract, it triggers exfoliation of the bladder epithelium. When mice harbored latent intracellular bladder
reservoirs of E.c., bladder exposures to G.v. triggered E.c. egress and rUTI at a 4-times higher rate compared
to exposures to vehicle alone or L.c. Importantly, G.v. exposures were cleared rapidly by the host and the
organism was absent by the time E.c. rUTI took place. These data demonstrate that exposures of the bladder to
vaginal bacteria can be transient, yet have a marked effect on bladder pathophysiology, and provide a potential
explanation for the link between BV and UTI. In this proposal, we will pursue two aims to understand how other
vaginal bacteria may promote or mitigate the negative effects of G.v. in the bladder. Aim 1 will investigate whether
L.c. can prevent G.v.-induced bladder exfoliation and E.c. rUTI. This is particularly relevant because L.c. is often
referred to in the recent literature as “protective” in the bladder based on clinical associations. Our studies will
address this possibility directly in an experimental system. Aim 2 will define how aspects of human vaginal
microbiome composition influence bladder exfoliation in women and examine how G.v. acts within native
communities to cause exfoliation and E.c. emergence in mice. Experiments in mice also will reveal whether
taxonomic groups in addition to G.v. contribute to these effects in the bladder. Successful completion of these
studies will uncover new paradigms in bacterial pathogenesis and provide novel insights that will inform future
efforts to treat and prevent rUTI.

## Key facts

- **NIH application ID:** 9958491
- **Project number:** 1R21AI152049-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Nicole Marie Gilbert
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $235,938
- **Award type:** 1
- **Project period:** 2020-02-20 → 2020-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9958491

## Citation

> US National Institutes of Health, RePORTER application 9958491, Roles of vaginal bacteria in bladder exfoliation and recurrent UTI (1R21AI152049-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9958491. Licensed CC0.

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