# Novel therapeutics for treatment of catheter-associated UTI and depletion of the vaginal reservoir

> **NIH NIH F30** · WASHINGTON UNIVERSITY · 2024 · $34,926

## Abstract

PROJECT SUMMARY / ABSTRACT
Antimicrobial resistance (AMR) contributes to an estimated 5 million deaths worldwide each year and is directly
responsible for over 1.2 million deaths. In the not-to-distant future, we may face a reality where infections
resistant to all existing antibiotics are commonplace. Therefore, addressing antimicrobial resistance by
developing antibiotic-sparing therapeutics is an urgent global health concern. Urinary tract infections (UTI)
drive over 15% of all antibiotic prescriptions and directly contribute to the development of AMR bacteria. One
potential antibiotic-sparing therapeutic for UTIs is monoclonal antibodies (mAbs), which have been
successfully deployed for decades and have a strong history of safety and efficacy. The objective of this
proposal is to develop mAbs to two types of UTIs that greatly contribute to global disease burden. The overall
hypothesis is that mAbs to bacterial pilus adhesin proteins will block adhesin-ligand interactions and thus
prevent bacterial adherence to host tissues. In Aim 1, mAbs will be explored as a treatment for catheter-
associated UTI (CAUTI) caused by two pathogens that are frequently multi-drug resistant: Enterococcus
faecalis and Acinetobacter baumannii. These bacteria cause CAUTI by using sticky adhesins to bind to
fibrinogen deposited on the surface of urinary catheters. mAbs will block this interaction to prevent catheter
colonization. In Aim 2, mAbs will be tested for their ability to block bacterial interaction with host tissue.
Uropathogenic Escheriscia coli (UPEC) frequently causes highly recurrent UTI (rUTI) in part by establishing
reservoirs in the gastrointestinal tract and vagina that serve as a source for UPEC’s continuous reintroduction
into the bladder lumen. While the adhesins responsible for gut colonization have been characterized, the
adhesin responsible for vaginal colonization is unknown. Based on existing data suggesting a role for the
UPEC S pilus in the vagina, the contribution of this pilus to vaginal colonization will first be elucidated. mAbs
will then be generated to the S pilus adhesin and tested for their ability to deplete UPEC from the vagina. The
long-term goal of the proposed research is to generate mAbs that can treat human urinary tract infections.
During the fellowship, the applicant will develop important skills for becoming an independent investigator of
infectious diseases. The sponsor of this work, Dr. Scott Hultgren, has vast experience studying urinary tract
infection pathogenesis and treatment, and the institutional environment provides supportive, collaborative
experts in microbiology and immunology. Washington University School of Medicine has a long history of
helping physician-scientists build successful careers. The proposed training plan will facilitate the applicant’s
transition into becoming an independent physician-scientist, using research to improve women’s health.

## Key facts

- **NIH application ID:** 10786057
- **Project number:** 5F30DK135390-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Morgan Rose Wilt Timm
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $34,926
- **Award type:** 5
- **Project period:** 2023-02-10 → 2026-02-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10786057

## Citation

> US National Institutes of Health, RePORTER application 10786057, Novel therapeutics for treatment of catheter-associated UTI and depletion of the vaginal reservoir (5F30DK135390-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10786057. Licensed CC0.

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