# Regulation of the Brucella abortus general stress response

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2024 · $486,450

## Abstract

Project Summary/Abstract
 The goal of this research proposal is to advance molecular-level understanding of a conserved
signal transduction system that influences the ability of Brucella abortus to survive chemical and physical
stress conditions, and to colonize mammalian hosts. The general stress response (GSR) signaling system
controls stress adaptation and chronic infection in a mammalian model of brucellosis. We are working to
understand how B. abortus detects environmental signals via a set of HWE-family histidine kinases to
influence infection. We have preliminary evidence that two sensor kinases coordinately control GSR
activation and infection in B. abortus. We have further discovered that previously uncharacterized genes
regulated by the GSR system – eipB, gsrN1 and gsrN2 – are determinants of mammalian infection. These
conserved genes protect Brucella spp. from cell envelope stress and control stress-dependent gene
expression at the post-transcriptional level, respectively.
 Investigation of these genes will define the molecular underpinnings of infection in an
understudied pathogen of significant human health and agricultural import. Given that sensor histidine
kinases are not present in mammals, the basic biochemical and genetic experiments we propose here
have the potential to inform new treatments for microbial infection targeted to sensory histidine kinases.
Proposed studies will be conducted by investigators that have expertise working on this select agent
under high containment BSL3 conditions. The specific aims of this project are:
1) Define the mechanism of stress signal detection by a multi-kinase sensory system
2) Characterize the mechanism by which EipB contributes to cell envelope function
3) Determine the mechanism by which the small RNAs GsrN1 and GsrN2 regulate Brucella
 infection biology

## Key facts

- **NIH application ID:** 10880935
- **Project number:** 1R01AI177619-01A1
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Sean Crosson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $486,450
- **Award type:** 1
- **Project period:** 2024-06-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880935

## Citation

> US National Institutes of Health, RePORTER application 10880935, Regulation of the Brucella abortus general stress response (1R01AI177619-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10880935. Licensed CC0.

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