# Nutritional immunity during Salmonella infection

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $387,500

## Abstract

SUMMARY
 Non-typhoidal Salmonella (NTS) cause a severe inflammatory diarrhea and infect
an estimated 100 million patients per year, of which 1.4 million are in the United States.
Although the early inflammatory response in the intestinal mucosa is critical to control
NTS infection and confine it to the gut, recent studies conducted by our group and others
have shown that elements of intestinal inflammation are exploited by NTS to thrive in the
inflamed gut and to transmit to naïve hosts. Multiple mechanisms - many of which are
still unknown - play a role in this process. In this regard, we found that sequestration of
essential metal ions, a process known as “nutritional immunity”, is an arm of the host
response that is exploited by NTS to thrive in the inflamed gut and to compete with the
intestinal microbiota. The primary objective of this application is to continue to elucidate
the mechanisms by which NTS thrive in the inflamed intestinal mucosa, evade the host's
nutritional immune response, and compete with the resident microbiota for metal
nutrients. Our central hypothesis is that NTS exploits nutritional immunity to outcompete
the microbiota for the essential metal micronutrients iron, zinc, and manganese. The
inflamed gut is a hostile environment where metal ion deprivation enhances the
proliferation of pathogens like NTS that can efficiently acquire metal ions. We reason
that understanding how NTS exploits nutritional immunity to its own advantage will lead
to new approaches to limit the replication of NTS in the inflamed gut and to impede its
transmission to other hosts. The proposed work is innovative because it establishes new
concepts on how a pathogen can exploit host mucosal defenses. It is our expectation
that the outcome of this study will identify mechanisms by which NTS, and likely other
pathogens or pathobionts, exploits nutritional immunity to thrive in the inflamed gut,
potentially leading to new therapies and vaccines to target metal ion acquisition by the
pathogen.

## Key facts

- **NIH application ID:** 9921201
- **Project number:** 5R01AI126277-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Manuela Raffatellu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,500
- **Award type:** 5
- **Project period:** 2016-05-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9921201

## Citation

> US National Institutes of Health, RePORTER application 9921201, Nutritional immunity during Salmonella infection (5R01AI126277-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9921201. Licensed CC0.

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