# Investigating phage therapy for the treatment of urinary tract infections

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2024 · $48,974

## Abstract

Urinary tract infections (UTIs) are responsible for a large public health burden with over half of women
experiencing a UTI during their lifetime. These infections, primarily in women, older adults, and those with
underlying conditions such as diabetes, are responsible for over $3.5 billion in health care costs annually in the
USA alone. The majority of UTIs are caused by uropathogenic E. coli (UPEC) and are readily treated with
antibiotics. However, global rise of antibiotic resistance amongst bacterial pathogens threatens the utility of the
current standard of care. Furthermore, up to 30% of UPEC UTIs will have recurrence within 6 months of treatment
due to intracellular UPEC reservoirs that are hidden from antibiotic therapy. Because of these reasons,
alternatives to antibiotics are desperately needed. Bacteriophages (phage), viruses that infect bacteria, have
long been hypothesized as a treatment for bacterial infection, predating the use of antibiotics by over a quarter
of a century. Unfortunately, like antibiotics, bacteria can become resistant to phage. Preliminary work has
identified several phage-resistant UPEC harboring mutations in lipopolysaccharide (LPS). These bacteria,
although capable of evading phage, are poorer at growing in urine and at colonizing the bladder than their
parental strains. The exact reason(s) for these fitness defects, however, are unknown. This work also aims to
assess the utility of phage for treating intracellular UPEC reservoirs, which are untouched by antibiotic therapy,
and which lead to UTI recurrence. Published and preliminary data suggests phage can interact and be
internalized by bladder cells, although no group has tested the ability of phage to reduce intracellular UPEC
burdens. Taken together, this preliminary data supports the hypothesis that phage therapy, through driving
phage resistance that leaves bacteria less fit, and through phage interactions with the bladder, will be effective
at treating both intracellular and extracellular UTIs. This hypothesis will be investigated by the following specific
aims: 1) Identify mechanisms underlying decreased growth in urine and poor colonization of the murine bladder
in phage resistant (LPS mutant) UPEC, 2) Characterize phage binding and internalization by the uroepithelium,
reduction of intracellular reservoirs, and stimulation of bladder immune responses. In investigating these aims,
several innovative tools such as primary bladder cell-derived organoids, super-resolution microscopy, and in vivo
mouse models of disease and phage therapy will be used. This proposal will provide the candidate with training
in UTI animal models, advanced microscopy techniques, protein isolation, and bladder organoid models. This
training, along with excellent mentorship and career development goals, will provide the candidate with the
necessary skills for an independent research career studying novel translational treatments for infectious
disease. This training will take pl...

## Key facts

- **NIH application ID:** 10817688
- **Project number:** 5F31DK136201-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Jacob Jeffrey Zulk
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2023-08-09 → 2025-08-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817688

## Citation

> US National Institutes of Health, RePORTER application 10817688, Investigating phage therapy for the treatment of urinary tract infections (5F31DK136201-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10817688. Licensed CC0.

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