# Investigating SloR virulence gene metalloregulation in Streptococcus mutans

> **NIH NIH R01** · MIDDLEBURY COLLEGE · 2021 · $370,860

## Abstract

PROJECT SUMMARY/ABSTRACT
Streptococcus mutans-induced caries formation continues to be a major problem in developed and developing nations,
which according to the World Health Organization, impacts 60-90% of children worldwide (63). Despite
widespread water fluoridation and the implementation of educational programs aimed at improving oral health in
the United States and abroad, recent reports reveal no significant improvement in the prevalence or severity of
caries in the primary dentition (64). In addition, nearly 100% of adults either have or have had caries in their
permanent teeth, contributing to the world's estimated direct costs for dental treatment that totaled $298 billion in
2010 (31, 64, 65).
 The survival and cariogenic potential of S. mutans in the human oral cavity is directly related to the
availability and transport of essential metal ions, particularly iron and manganese (11, 12, 48, 55). In the present
grant application, we profess a novel approach to alleviating tooth decay that is centered on investigating virulence
gene regulation by the S. mutans SloR metalloregulatory protein. During the previous grant term, we confirmed
SloR-dependent repression of S. mutans metal ion transport genes and virulence factors when sustainable levels of
manganese are achieved (such as during a mealtime), and loss of this repression when metal ions become limiting
(such as between meals). These observations led us to propose that modifications to SloR that render it
constitutively repressive regardless of exogenous manganese availability can significantly attenuate S. mutans
virulence gene expression and impede the process of cariogenesis. This application sets out to address this
hypothesis by elucidating the structural basis for SloR activation and DNA binding in S. mutans using molecular,
biochemical, and next-generation sequencing approaches. The proposed research is highly significant because it can
lead to an improved understanding of metal ion homeostasis in S. mutans and lend support to the growing body of
evidence that implicates regulators of bacterial metal ion uptake/transport as key therapeutic targets (1, 4, 8, 35, 37,
40, 43). Moreover, these studies can reveal the mechanisms that underlie the inherent ability of S. mutans to regulate
virulence gene expression in the human mouth where significant changes in metal ion availability, acid pH and
oxidative stress are part of its obligate biofilm lifestyle.

## Key facts

- **NIH application ID:** 10210251
- **Project number:** 5R01DE014711-14
- **Recipient organization:** MIDDLEBURY COLLEGE
- **Principal Investigator:** Grace A. Spatafora
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $370,860
- **Award type:** 5
- **Project period:** 2004-07-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10210251

## Citation

> US National Institutes of Health, RePORTER application 10210251, Investigating SloR virulence gene metalloregulation in Streptococcus mutans (5R01DE014711-14). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10210251. Licensed CC0.

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