# Central metabolism of Salmonella in the inflamed gut

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $65,132

## Abstract

PROJECT SUMMARY
 
Infection with the bacterial pathogen Salmonella enterica serovar Typhimurium (S. Tm)
results in acute inflammatory diarrhea. S. Tm invades the intestinal epithelium and
replicates in the tissue phagocytes, triggering a potent mucosal inflammatory response
aimed at clearing the invading bacteria. Intriguingly, intestinal inflammation results in an
expansion of the S. Tm population in the gut lumen. The molecular mechanisms
underlying the outgrowth of S. Tm over the indigenous microbiota remains largely
unknown. Our central hypothesis is that the inflamed gut constitutes a peculiar nutritional
environment that enables S. Tm to outgrow competing commensal microbes. We will
test key aspects of our hypothesis by pursuing the following specific aims: 1.) Determine
the contribution of the electron donor formate to growth of S. Tm in the inflamed gut
lumen and test the working hypothesis that inflammation perturbs syntrophic
relationships between formate-producing and -consuming microbes, allowing S. Tm to
access the formate pool during growth in the inflamed gut. 2.) Determine how host-
derived electron acceptors alter regulation of the TCA cycle and explore potential
consequences. Successful completion has a strong potential to have a high impact on
gastroenteritis research by providing a novel concept, i.e. that an enteric pathogen
exploits metabolites from both, the host (electron acceptors) and the microbiota
(fermentation end products). We envision that a better understanding of the mechanisms
by which S. Tm outgrows competing microbes during inflammation will aid the
development of new and innovative approaches for treatment.

## Key facts

- **NIH application ID:** 10112996
- **Project number:** 3R01AI118807-07S1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Sebastian E Winter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,132
- **Award type:** 3
- **Project period:** 2015-05-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112996

## Citation

> US National Institutes of Health, RePORTER application 10112996, Central metabolism of Salmonella in the inflamed gut (3R01AI118807-07S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10112996. Licensed CC0.

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