# MucR gene silencing and Brucella virulence

> **NIH NIH R21** · EAST CAROLINA UNIVERSITY · 2020 · $218,927

## Abstract

PROJECT SUMMARY
 The Zn finger protein MucR is a global regulator of gene expression in the α-proteobacteria, and a major
virulence determinant in Brucella. Despite this importance, surprisingly little is known about how MucR
functions at the molecular level beyond the fact that its works predominantly as a transcriptional repressor. We
have recently obtained evidence suggesting that MucR serves as an H-NS-like gene silencer in Brucella. This
proposed function is consistent with the role that MucR homologs play in other α-proteobacteria, where they
work in concert with antagonistic transcriptional activators to coordinate the proper temporal expression of
virulence and symbiosis genes. But demonstrating that the Brucella MucR is an authentic H-NS-like gene
silencer would represent a newly described function for a bacterial Zn finger protein.
 The studies proposed in this application will – a) utilize chromatin immunoprecipitation massively parallel
DNA sequencing (ChIP-seq) and RNA sequencing (RNA-seq) to identify the direct targets of MucR repression
in B. abortus 2308; b) employ genetic and biochemical strategies to test the hypothesis that MucR functions as
an H-NS-like gene silencer; and c) use cellular and mouse models to test the hypothesis that MucR silencing
of specific genes is required for wild-type virulence. If these hypotheses are supported, the proposed studies
will define a novel class of bacterial gene silencers, greatly improve our understanding of how Zn finger
proteins function in prokaryotic biology, and provide an explanation for why MucR is such an important
virulence determinant in Brucella.
 Successful completion of the proposed studies should also yield information useful for developing improved
strategies for preventing and treating human brucellosis, a zoonosis of world-wide importance. There are
currently no vaccines that can be safely and effectively used to prevent this disease, and treatment requires
prolonged administration of two antibiotics. The extreme and stable attenuation displayed by Brucella mucR
mutants makes them attractive as novel vaccine candidates, and the fact that MucR is structurally distinct from
eukaryotic Zn finger proteins makes it a viable drug target.

## Key facts

- **NIH application ID:** 9872108
- **Project number:** 5R21AI141438-02
- **Recipient organization:** EAST CAROLINA UNIVERSITY
- **Principal Investigator:** ROY M ROOP
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $218,927
- **Award type:** 5
- **Project period:** 2019-02-13 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872108

## Citation

> US National Institutes of Health, RePORTER application 9872108, MucR gene silencing and Brucella virulence (5R21AI141438-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9872108. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*