# Potentiation of fluoride toxicity in oral pathogens

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $195,000

## Abstract

PROJECT SUMMARY/ABSTRACT
The problem: Dental caries is the leading health condition worldwide, affecting billions of people and causing
pain, impaired nutrition and social functioning, reduction in work/school productivity, and significant economic
impacts. For the most vulnerable groups, such as children and older adults, and individuals with high caries
risk of all ages, the consequences of this disease – including a reduced quality of life, morbidity and even
mortality – are unacceptable. Because caries is caused by the metabolism of dietary sugars by a cariogenic
biofilm, it is very difficult to control; the widespread consumption of fermentable sugars in modern diets favors
cariogenic species such as Streptococcus mutans and the opportunistic fungi Candida albicans in the dental
biofilm, perpetuating the caries process. Fluoride is the most effective agent for caries control, but it has very
limited antimicrobial effects because most microbes have membrane proteins to expel fluoride and keep
intracellular concentrations at sub-inhibitory levels. Different oral microbial species possess different types of
fluoride exporters; S. mutans and C. albicans employ CLCF and FEX proteins, respectively, while beneficial
oral streptococci use Fluc proteins. This creates an opportunity to specifically target pathogenic oral microbes
to modify species dynamics towards health-associated symbiotic communities in biofilms exposed to sugar and
fluoride. Hypothesis: We hypothesize that fluoride export proteins can be targeted for antimicrobial
development against cariogenic oral bacteria and fungi, while leaving beneficial oral microbiota intact. This
hypothesis will be tested in the following specific aims: S.A.#1: To evaluate the competitive fitness of fluoride
export-deficient strains of S. mutans and C. albicans in mixed-species biofilms under conditions of changing
fluoride and pH; S.A.#2: To identify natural products that potentiate fluoride toxicity for pathogenic oral
microbiota. Significance: The results of these studies will establish groundwork for the development of novel
caries treatments that potentiate the antimicrobial effects of fluoride ion, as well as provide new basic
knowledge about the role of fluoride and microbial fluoride resistance mechanisms in community dynamics of
the oral microbiota.

## Key facts

- **NIH application ID:** 10792920
- **Project number:** 5R21DE032837-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Randy B. Stockbridge
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $195,000
- **Award type:** 5
- **Project period:** 2023-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10792920

## Citation

> US National Institutes of Health, RePORTER application 10792920, Potentiation of fluoride toxicity in oral pathogens (5R21DE032837-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10792920. Licensed CC0.

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