# BrpA in Virulence Modulation of Streptococcus mutans

> **NIH NIH R01** · LSU HEALTH SCIENCES CENTER · 2022 · $515,763

## Abstract

SUMMARY
Despite substantial progress in prevention and treatment, dental caries, commonly known as tooth decay
or cavities, remains one of the most common and costly infectious diseases worldwide. According to the
CDC, associated health care costs USA tens of billions of dollars annually. Novel, comprehensive
strategies are needed to effectively combat caries pathogenesis. Cariogenic bacteria form tenacious
biofilms on the surface of teeth known as dental plaque. Supported by R01 DE019452, we have over the
past six years generated seminal evidence that biofilm regulatory protein BrpA, a multi-functional surface-
associated protein, plays a critical role in regulation of Streptococcus mutans cell envelope biogenesis and
biofilm formation and its ability to cause carious lesions. The overall goals of this competitive renewal are to
uncover the complexity of the molecular mechanisms that govern the expression of brpA and the
mechanisms how BrpA mediates intra- and inter-species biofilm formation, and to explore the potential of
the lead small molecules in targeting BrpA and modulation of S. mutans virulence. We will use an
integrative approach including various modern molecular, biochemical and bioinformatics techniques to
identify the transcriptional and post-transcriptional factors that govern the regulation of brpA expression,
and to determine the different binding epitopes and build the ligand-protein complex model to guide
structural and functional analysis of BrpA. In addition, we will use organic chemistry along with various
function assays and in vivo rat caries model to optimize the efficacy and selectivity of the selected lead
small inhibitory molecules against S. mutans and to explore their potential in novel anticaries strategy.
Successful implementation of this proposal could prove to be major advances in our understanding of BrpA
in S. mutans pathophysiology, which could ultimately be applied to the LCP proteins in other Gram-positive
bacteria. The findings on small molecules are expected to provide a solid foundation for the development of
novel strategies against S. mutans and human dental caries.

## Key facts

- **NIH application ID:** 10539743
- **Project number:** 2R01DE019452-10
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** ZEZHANG TOM WEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $515,763
- **Award type:** 2
- **Project period:** 2009-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10539743

## Citation

> US National Institutes of Health, RePORTER application 10539743, BrpA in Virulence Modulation of Streptococcus mutans (2R01DE019452-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10539743. Licensed CC0.

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