# Inhibition of Streptococcus mutans by oral commensal streptococci and nitrie-mediated activity

> **NIH NIH R00** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $249,666

## Abstract

Project Summary/Abstract
Streptococcus mutans is the major etiological agent of dental caries, the most prevalent infectious disease
world-wide. Biofilm formation by the cariogenic bacterium S. mutans is crucial for the pathogenesis of dental
caries. Preventing or successfully treating severe caries remains an elusive task. The conventional treatment
for dental caries usually involves the mechanical removal of dental biofilms, the use of antibiotics, or invasive
procedures. However, these treatments are sometimes ineffective and the use of antibiotics or invasive
procedures can result in the development of drug resistant pathogens or complications. Therefore, an
alternative and less invasive approach is needed. Interestingly, the oral cavity exhibits higher concentrations of
nitrite than other body sites. Elevated concentrations of nitrite in the oral cavity have been associated with a
reduced prevalence of dental caries, suggesting that nitrite may be an alternative therapeutic for the treatment
of caries. However, the exact mechanism(s) of how nitrite interferes with the biofilm formation and
pathogenesis of S. mutans is unknown. The oral cavity harbors hundreds of bacterial species and they interact
with each other and contribute to health and disease status of the oral cavity. Our preliminary data
demonstrate that the hydrogen peroxide-producing oral commensal Streptococcus parasanguinis, inhibits S.
mutans growth and biofilm formation in the presence of nitrite, revealing a new anti-infection strategy by the
commensal oral streptococcus. In order to develop nitrite-containing therapeutics to treat dental caries, it is
critical to understand mechanisms of S. mutans nitrite resistance. Transposon mutagenesis of S. mutans
identified mutants that are resistant to S. parasanguinis and nitrite-mediated activity. One mutant is mapped to
a gene coding for a histidine kinase (SMU.486). This histidine kinase and its response regulator (SMU.487)
are homologous to a nitrite sensing two-component regulatory system in Escherichia coli, suggesting that they
may mediate inhibition of S. mutans by S. parasanguinis and nitrite. Therefore, the immediate goal of this
research proposal is to investigate how the nitrite sensing two-component system SMU.486 and SMU.487
mediate S. mutans’ response to nitrosative stress and identify nitrosative stress response pathways controlled
by SMU.486 and SMU.487. RNA-sequencing/transcriptomics will be used to analyze how SMU.486 and
SMU.487 contribute to nitrosative stress resistance. In addition, the proposal will examine the ability of S.
parasanguinis and nitrite-mediated activity to inhibit S. mutans and prevent caries in an animal model of dental
caries. During this time the candidate will complete mentored training in Oral Microbiology, RNA
sequencing/transcriptomics, and other professional development activities. The mentored training will prepare
the candidate for the independent R00 phase in which the candidate will ...

## Key facts

- **NIH application ID:** 9981417
- **Project number:** 5R00DE025913-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Jessica A Scoffield
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,666
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981417

## Citation

> US National Institutes of Health, RePORTER application 9981417, Inhibition of Streptococcus mutans by oral commensal streptococci and nitrie-mediated activity (5R00DE025913-05). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9981417. Licensed CC0.

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