# Mechanisms of persistent Salmonella infection

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $452,116

## Abstract

ABSTRACT
Host-adapted strains of Salmonella enterica cause systemic infections and have the ability to persist systemically
within granulomas for long periods of time. Persistently infected hosts are often asymptomatic and transmit
disease to naïve hosts, thereby serving as a critical reservoir for disease. From the bacterial perspective,
persistent infection is essential for microbial survival in nature. However, very little is known about the molecular
mechanisms involved in persistent Salmonella infections and transmission between mammalian hosts.
Increased knowledge of the molecular mechanisms of Salmonella persistence may lead to the ability to eradicate
the Salmonella carrier state pharmacologically. Our long-term goal is to understand how Salmonella
persists within tissues of mammalian hosts for preventive and therapeutic purposes. The objective of this
proposal, which is our next step in pursuit of this goal, is to identify host pathways involved in granuloma
dynamics and to determine how Salmonella manipulates host cells for long-term survival. The premise that will
be tested in this application is that Salmonella injects virulence factors into granuloma macrophages that both
promote an anti-inflammatory state and block specific proinflammatory responses in order to persist in
mammalian hosts. We propose to study the molecular mechanisms of persistent Salmonella infections in
granulomas of mammalian hosts. Aim 1 will characterize the cellular organization and molecular regulation of
granulomas during persistent Salmonella mouse infection, with a particular focus on visualization and analysis
of gene expression of granuloma macrophages in tissue sections by spatial transcriptomics. In Aim 2, we will
identify mechanisms of Salmonella-dependent manipulation of granuloma macrophages. Aim 3 will characterize
the role of the Type 6 secretion system during persistent Salmonella infection. The proposed research is
innovative because we investigate the spatial transcriptomics of granuloma macrophages, a heretofore-
unexamined pathogen niche. Insight into host-pathogen interactions during persistent infection of a mammalian
host is impactful as novel biomarkers and treatments of asymptomatic carriers are needed for eradication of this
disease reservoir.

## Key facts

- **NIH application ID:** 10510554
- **Project number:** 5R01AI116059-08
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Denise M Monack
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $452,116
- **Award type:** 5
- **Project period:** 2014-11-01 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10510554

## Citation

> US National Institutes of Health, RePORTER application 10510554, Mechanisms of persistent Salmonella infection (5R01AI116059-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10510554. Licensed CC0.

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