# Mechanisms of methylthioadenosine signaling during Salmonella infection

> **NIH NIH F31** · DUKE UNIVERSITY · 2020 · $37,668

## Abstract

Project Summary/Abstract:
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a leading cause of gastroenteritis and non-
typhoidal bacteremia worldwide. Previous work from our lab has demonstrated that the metabolite,
methylthioadenosine (MTA), is able to module the host response to S. Typhimurium. My recent work
demonstrated that the molecule serves a second role during S. Typhimurium invasion in which MTA directly
suppresses S. Typhimurium virulence by repressing the Salmonella Pathogenicity Island-1 and the flagella
regulon. This in turn suppresses the ability for the bacteria to invade cells in the gut, induce inflammation, and
results in reduced in vivo virulence. While my recent publication described this phenomenon, the mechanism by
which MTA is sensed by S. Typhimurium and suppresses bacterial virulence remains unknown. Further, while
we have described that concentrations of MTA change in serum during Salmonella infection, we have not
previously explored the possibility that the concentrations of this metabolite change in the gut during a natural
model Salmonella infection. If the metabolite is present at different concentrations in the gut during infection, it
is unknown whether these changes in concentration have consequences on the bacteria’s ability to successfully
colonize the gut. This proposal will address my hypothesis that host MTA can shape disease outcomes
by suppressing S. Typhimurium virulence during infection. This would represent a novel example of host-
pathogen cross-talk shaping infection outcomes in the gut.
The purpose of this grant is to develop a mechanistic understanding of how S. Typhimurium senses and
responds to MTA, and to explore the implications of this sensing on host-pathogen cross-talk during infection.
To address this, I will measure spatial and temporal MTA regulation along the murine gut and test the ability for
host-produced MTA to suppress S. Typhimurium virulence in vivo. I will then pair proteomic, genomic, and
transcriptomic approaches to elucidate the molecular mechanisms that enable MTA mediated suppression of S.
Typhimurium virulence. Together, these findings will inform the long term goal of this project- which is to to
understand how manipulating host and/or bacterial methionine metabolism could be leveraged to improve
Salmonella infection outcomes.

## Key facts

- **NIH application ID:** 9980693
- **Project number:** 5F31AI143147-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Jeffrey Bourgeois
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,668
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980693

## Citation

> US National Institutes of Health, RePORTER application 9980693, Mechanisms of methylthioadenosine signaling during Salmonella infection (5F31AI143147-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980693. Licensed CC0.

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