# The roles of fosfomycin resistant subpopulations of Escherichia coli in urinary tract infection.

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2024 · $29,058

## Abstract

PROJECT SUMMARY/ABSTRACT
Urinary tract infections (UTIs) are one of the most common bacterial infections worldwide and the bacteria that
cause them are becoming increasing resistant to frontline antibiotics. As a result, last resort antibiotics, like
fosfomycin, are beginning to be more frequently prescribed. Uropathogenic Escherichia coli (UPEC), which is
the primary cause of UTIs, can become resistant to fosfomycin, through mutations that impair the function or
production of the UhpT transporter, which imports fosfomycin into the bacterial cell. The current paradigm is
that such mutations come at a fitness tradeoff because impairment of UhpT limits the import of the glycolysis
intermediate glucose-6-phosphate. However, my preliminary data indicate that mutations that lead to
increased resistance to fosfomycin by abrogating uhpT expression, do not impede colonization of the host
urinary tract. In fact, loss of fosfomycin import demonstrates increased persistence during long-term infection.
Additionally, I have shown that 77% of screened UPEC clinical isolates harbor fosfomycin resistant
subpopulations. This raises the alarming hypothesis that fosfomycin resistant subpopulations arise
during UTI, possibly in response to a host-imposed stress and may provide additional fitness
advantages for the pathogen. I will test this hypothesis through two specific aims which will: determine the
contribution of fosfomycin resistant subpopulations to UPEC pathogenesis (Aim 1) and elucidate the basis of
prolonged bacteriuria during UPEC pathogenesis following loss of uhpBA (Aim 2). Together my studies will
provide insights that will ultimately help us curb the onset and propagation of resistance to one of the last-
resort antibiotic agents, by thoroughly elucidating novel mechanisms that lead to fosfomycin resistance during
infection and gauging their fitness advantages and disadvantages in comparison to their parental strains.
Through the execution of these aims, I will cultivate valuable skills in genomic analysis, advanced microscopy
techniques, eukaryotic cell culture, and comprehensive analysis of host-pathogen interactions.

## Key facts

- **NIH application ID:** 10976407
- **Project number:** 5F31AI174488-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Tomas Alexander Bermudez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $29,058
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10976407

## Citation

> US National Institutes of Health, RePORTER application 10976407, The roles of fosfomycin resistant subpopulations of Escherichia coli in urinary tract infection. (5F31AI174488-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10976407. Licensed CC0.

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