# Characterizing the impact of small regulatory RNAs on the virulence of Brucella spp.

> **NIH NIH R21** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2021 · $235,576

## Abstract

Project Summary
 Brucella spp. are bacteria that naturally infect a variety of domesticated and wild animals leading to
abortions and sterility, and these bacteria are also capable of causing debilitating human infections, which
often result from human exposure to infected animals and animal products. Brucella spp. are considered
threats as potential biological weapons. Importantly, antibiotic treatment against brucellosis is prone to disease
relapse, and there is currently no safe and effective vaccine to protect humans against infection with Brucella.
The brucellae are intracellular pathogens that reside within immune cells called macrophages where they
replicate in a specialized compartment, and the capacity of Brucella to survive and replicate within
macrophages is essential to their ability to cause disease. Over the last few years, our laboratory has
characterized genetic pathways that are critical for the intracellular survival and pathogenesis of Brucella
strains, and specifically, we have identified small regulatory RNAs (sRNAs) that are essential for Brucella
virulence.
 Preliminary experiments have revealed the presence of more than 20 novel sRNAs in B. abortus, and we
have identified one of these sRNAs, called Bsr18 (for Brucella small RNA) that is required for the for virulence
of B. abortus in a mouse model of chronic Brucella infection. We hypothesize that Bsr18 is produced under
biologically relevant conditions, such as acidic pH, oxidative stress, nutrient limitation, and/or diminished
oxygen, and moreover, we hypothesize that Bsr18 is required for the ability of B. abortus to cope with these
conditions. Additionally, it is hypothesized that Bsr18 regulates the expression of genes important for the
infectivity of B. abortus. Therefore, we plan to characterize the biological and regulatory functions of Bsr18, and
in the end, the information gleaned from these studies may be used to develop new therapeutic and vaccine
strategies against human Brucella infection.

## Key facts

- **NIH application ID:** 10228752
- **Project number:** 5R21AI149124-02
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Clayton C Caswell
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $235,576
- **Award type:** 5
- **Project period:** 2020-08-05 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10228752

## Citation

> US National Institutes of Health, RePORTER application 10228752, Characterizing the impact of small regulatory RNAs on the virulence of Brucella spp. (5R21AI149124-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10228752. Licensed CC0.

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