# Central metabolism of Salmonella in the inflamed gut

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $479,541

## Abstract

PROJECT SUMMARY
Infection with the bacterial pathogen Salmonella enterica serovar Typhimurium (S. Tm) is a common cause of
inflammatory diarrhea. Intriguingly, intestinal inflammation drives an expansion of the S. Tm population in the
gut lumen. The molecular mechanisms that support S. Tm colonization of the intestinal tract remain
incompletely understood. Our central hypothesis is that the inflamed gut constitutes a peculiar nutritional
environment that enables S. Tm to outgrow obligate anaerobic commensal bacteria. We have recently
demonstrated that during the acute phase of the infection, neutrophil-derived electron acceptors facilitate an
oxidative central metabolism in S. Tm. In this application, we hypothesize that S. Tm relies on a branched TCA
cycle for initial gut colonization. In particular, tartaric acid, produced through oxidation of microbiota-liberated
sugars, supports fumarate reduction in the branched TCA cycle. We will test key aspects of our hypothesis by
pursuing the following specific aims: 1.) determine how utilization of D- and L-tartrate contributes to growth of
S. Tm in the lumen of the mammalian large intestine, 2.) determine the origin of tartrate during S. Tm infection,
and 3.) investigate the regulation of tartrate utilization genes in vitro and in vivo. This work will advance our
understanding of how intestinal pathogens, such as S. Tm, adapt their carbon and energy metabolism to
colonize the mammalian intestinal tract. 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:** 10074508
- **Project number:** 5R01AI118807-07
- **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:** $479,541
- **Award type:** 5
- **Project period:** 2015-05-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074508

## Citation

> US National Institutes of Health, RePORTER application 10074508, Central metabolism of Salmonella in the inflamed gut (5R01AI118807-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10074508. Licensed CC0.

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