# A bacterial biosensor for intracellular metal availability in the gut

> **NIH NIH R21** · WASHINGTON STATE UNIVERSITY · 2022 · $58,546

## Abstract

PROJECT SUMMARY
Of the foodborne bacterial, protozoal and viral diseases, non-typhoidal Salmonella enterica cause the largest
burden of illness and death worldwide. The most common human clinical isolates are Salmonella enterica
serovars Typhimurium (S. Typhimurium, STm) and Enteriditis (S. Enteriditis). Infection can cause either a self-
limiting gastroenteritis or a life-threatening, invasive disease in immunocompromised individuals. During enteric
infection, STm adopts both extracellular and intracellular lifestyles, colonizing the intestinal lumen as well
epithelial cells and phagocytes in the intestinal mucosa. Here we will study how host-mediated restriction of
transition metals, known as nutritional immunity, affects STm colonization of the gut. The NRAMP family of
proteins are “promiscuous” transporters of divalent cations that play a major role in metal ion homeostasis from
bacteria to man. In mammals, there are two NRAMP genes, SLC11A1 and SLC11A2 in humans and Slc11a1
and Slc11a2 in mice. Slc11a1 is restricted to the myeloid lineage whereas Slc11a2 is ubiquitously expressed.
Whilst the role of Slc11a1 in controlling intracellular bacterial and parasitic infections in macrophages and mice
is undisputed, whether Slc11a2 also contributes to antimicrobial functions is unknown. Our general hypothesis
is that intracellular metal ion availability differs in epithelial cells and phagocytes in the gut due to the distinct
cell-type expression of SLC11A1 and SLC11A2. First, we will use microbial biosensors of metal ion
concentrations to infect bovine ligated ileal loops, a highly relevant model of enteric salmonellosis in humans,
and map the spatiotemporal distribution of metal ion deprivation in the gut. Second, we will define whether
SLC11A2, the sole NRAMP family member expressed in intestinal epithelial cells, defends against invading
pathogens via metal nutrient limitation. Completion of this proposal will close a significant knowledge gap about
host-microbe competition for metal ions in the gut during enteric infection.

## Key facts

- **NIH application ID:** 10353307
- **Project number:** 1R21AI166152-01
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Leigh Knodler
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $58,546
- **Award type:** 1
- **Project period:** 2022-04-22 → 2022-12-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10353307

## Citation

> US National Institutes of Health, RePORTER application 10353307, A bacterial biosensor for intracellular metal availability in the gut (1R21AI166152-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10353307. Licensed CC0.

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