# Applied Metatranscriptomics and Metatranslatomics to identify new mechanisms of Salmonella-microbiota competition

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $223,997

## Abstract

SUMMARY
The pathogen Salmonella enterica serovar Typhimurium (STm) exploits aspects of host immunity to establish a
niche in the gut and outcompete the resident microbiota. Despite significant progress in understanding the
competitive dynamics between STm and the gut microbiota, there remain gaps in our knowledge regarding the
specific mechanisms involved in their interactions. Herein, we propose a combined approach that integrates
metagenomic (metaG), metatranscriptomic (metaT), and metatranslatomic (metaRS) profiles to elucidate new
mechanistic interactions between STm and the gut microbiota. Specifically, we will use quantitative metaG,
metaT, and integrate innovative community-level ribosome footprinting (metaRS) to construct a comprehensive
profile of resource allocation and substrate preferences within the gut microbiota. It is our expectation that these
combined approaches will lend insight into how metabolic niches are perturbed by STm colonization and
associated host immune responses. Through the integration of these multiomics, we have generated testable
hypotheses regarding potential mechanisms of competition between STm and the gut microbiota. We intend to
test these hypotheses in this research application. Our central hypothesis is that elucidating microbial
metabolism in the gut, in conjunction with the analysis of host responses, will unveil new competitors and
mechanisms of competition between STm and the gut microbiota. We will test our hypothesis by pursuing two
Specific Aims: In Aim 1, we will analyze bacterial metabolism to identify potential Salmonella competitors in mice
and test the predictions in vitro and in vivo. We will validate the preliminary finding that STm infection depletes
specific members of the microbiota with similar metabolic profiles. We will also test the prediction that metabolic
overlap between STm and specific members of the microbiota reflects competition for resources in the gut. In
Aim 2, we will investigate whether host antimicrobial responses promote Salmonella competition with selected
members of the gut microbiota. Collectively, this study will provide a comprehensive analysis of bacterial
metabolism in the gut and how this is perturbed in the context of STm infection. Moreover, the study will test
hypotheses stemming from our preliminary data as well as generate and test new hypotheses concerning
mechanisms governing microbial competition, also in the context of host responses. Moving forward, the insights
garnered from this research hold promise for therapeutic interventions aimed at reducing STm colonization and
reinstating intestinal homeostasis.

## Key facts

- **NIH application ID:** 10976148
- **Project number:** 1R21AI186034-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Manuela Raffatellu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $223,997
- **Award type:** 1
- **Project period:** 2024-05-16 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10976148

## Citation

> US National Institutes of Health, RePORTER application 10976148, Applied Metatranscriptomics and Metatranslatomics to identify new mechanisms of Salmonella-microbiota competition (1R21AI186034-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10976148. Licensed CC0.

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