# Regulation of Salmonella Virulence bythe PhoP Protein

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $501,819

## Abstract

PROJECT SUMMARY
Pathogens harbor virulence genes, which are required to cause disease. Paradoxically,
pathogens also harbor anti-virulence genes, which restrict virulence potential. Anti-
virulence genes likely play roles in chronic infection and transmission to new hosts.
Understanding the interplay between virulence and anti-virulence genes will define the
full range of variables that directly impact the progression of disease. This proposal
seeks such understanding by focusing on the mgtCBR virulence operon of the
facultative intracellular pathogen Salmonella enterica serovar Typhimurium, which
specifies the F1Fo ATP synthase inhibitor MgtC, the Mg2+ transporter MgtB, and the
MgtR peptide that promotes MgtC degradation. Homologs of the mgtC and/or mgtB
genes are required for virulence in important human pathogens, including
Mycobacterium tuberculosis, Burkholderia cenocepacia, Brucella suis, Yersinia pestis,
Pseudomonas aeruginosa, and S. enterica serovars Typhi and Typhimurium. We propose
to investigate how novel genetic elements control the temporal display of virulence, and
how Salmonella regulates an anti-virulence trait. Specifically, we will explore the
biochemical function and physiological role of two novel genes that modify the levels,
activities and/or availability of the MgtC and MgtB virulence proteins. In addition, we
will seek to understand how the structural protein MgtC enhances the levels of active
PhoP, the master regulator of Salmonella virulence and transcriptional activator of the
mgtC gene. Finally, we will explore the mgtCBR-mediated physiological changes that
promote tolerance to antibiotics. The proposed research will reveal new concepts in
bacterial pathogenesis applicable to various organisms and disease conditions.

## Key facts

- **NIH application ID:** 9916691
- **Project number:** 5R01AI049561-29
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Eduardo Groisman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $501,819
- **Award type:** 5
- **Project period:** 1992-02-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9916691

## Citation

> US National Institutes of Health, RePORTER application 9916691, Regulation of Salmonella Virulence bythe PhoP Protein (5R01AI049561-29). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9916691. Licensed CC0.

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