# Characterization of pathogen nutrient acquisition and transport systems required during UTI

> **NIH NIH F32** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $2,500

## Abstract

Project Abstract
Urinary tract infection (UTI) represents a substantial burden in the United States generating over 11 million
clinic visits and costing $3.5 billion annually. Uropathogenic Escherichia coli (UPEC) is the causative organism
for 80% of uncomplicated UTI cases that are currently treated with antibiotics; it is becoming increasingly
evident that other treatments are needed. These treatments will be especially important for the 4 million U.S.
women who suffer recurrent UTI and are given long term antibiotic regimens, which in turn fuels increasing
antibiotic resistance. There is currently a major gap in the understanding of how UPEC obtain the nutrients
needed to rapidly replicate inside the host, as well as knowledge of specific growth compounds that promote
successful colonization. The urinary tract is a harsh and nutrient-restricted environment; therefore, bacterial
pathogens must adapt their nutrient uptake and corresponding metabolic pathways to best utilize available
resources. In contrast to E. coli in the intestinal tract, UPEC in the bladder is thought to utilize amino acids as a
primary carbon source. Guided by preliminary data, this proposed study will work toward the long-term goal of
achieving a better understanding of UPEC biology to encourage the development of improved UTI treatments.
My central hypothesis is that specific UPEC transport systems are required during UTI to facilitate metabolic
adaptation to the host urinary tract environment and allow for infection to occur. This hypothesis will be tested
by conducting two Specific Aims: 1) delineate transport systems that are crucial infection-specific fitness
factors for growth in human urine, and 2) identify transport systems that serve as fitness factors during UTI in
vivo. This proposed study will characterize critical UPEC transport systems and identify metabolic pathways
that are dependent on the substrate being transported during infection. We have previously constructed,
identified, and ordered the required transposon mutants needed for this study. Under the first aim, transporter
mutants will be grown in human urine and nutrient-rich media to compare, and subsequently eliminate, mutants
with generalized growth defects to identify those with only growth defects in urine. Additionally, gene
expression profiles will be compared to identify the metabolic shifts that occur when essential nutrients are
eliminated from the milieu. Under the second aim, the well-established CBA/J murine model of ascending UTI
will be utilized to identify transport systems that serve as host-specific fitness factors during UTI in vivo (e.g.,
required during UTI but not required for growth in human urine). The contribution of individual transporters will
be assessed and ranked in an unbiased manner through a novel co-challenge technique utilizing qPCR to
quantify levels of mutant bacteria among small subpopulations of similar mutants. Phenotypic assays will be
performed on select transp...

## Key facts

- **NIH application ID:** 10653499
- **Project number:** 3F32AI147527-03S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Allyson E Shea
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,500
- **Award type:** 3
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10653499

## Citation

> US National Institutes of Health, RePORTER application 10653499, Characterization of pathogen nutrient acquisition and transport systems required during UTI (3F32AI147527-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10653499. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*