# Metabolomic Mechanisms of Nutritional Immunity in the Urinary Tract

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $340,015

## Abstract

PROJECT SUMMARY
Urinary tract infections (UTIs) are common, drive extensive antibiotic use, and are becoming increasingly
resistant to treatment. There is general agreement that urinary chemical composition influences UTI
pathogenesis, but this has been difficult to translate to clinical practice. Clinical urinary pathogens possess
numerous genetic adaptations to the urinary environment, suggesting multiple selective pressures related to
urinary composition. Recently, we identified individual differences in urine's ability to support antibacterial iron
chelation by the innate immune protein siderocalin (SCN; also known as Lipocalin-2 or NGAL). Using mass
spectrometry-based metabolomics and biochemical hypothesis-testing, we have mechanistically linked these
differences to a specific chemical class of human urinary metabolites. Here we will identify human urinary
metabolomic influences on SCN activity and other aspects of UTI pathogenesis. Because human urine is
chemically complex, we will combine recent bioanalytical advances with contemporary data science
approaches to identify metabolomic networks that influence bacterial growth and behavior. Our objective is to
identify networks associated with SCN activity and bacterial growth, explore their mechanism(s) of action, and
learn their physiologic origins as a basis for new prophylactic and therapeutic strategies. The proposed
analyses and experiments are a rigorous initial evaluation of the hypothesis that urinary composition influences
infection susceptibility and can be modified as a non-antibiotic therapy.

## Key facts

- **NIH application ID:** 9837435
- **Project number:** 5R01DK111930-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jeffrey P Henderson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $340,015
- **Award type:** 5
- **Project period:** 2017-12-26 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9837435

## Citation

> US National Institutes of Health, RePORTER application 9837435, Metabolomic Mechanisms of Nutritional Immunity in the Urinary Tract (5R01DK111930-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9837435. Licensed CC0.

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