# Pyruvate oxidase: a molecular determinant of commensalism among the oral microbiome

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $500,980

## Abstract

Project Summary
Caries is one of the most prevalent oral diseases. Despite several decades of substantial caries
research, only incremental progress has been made in disease prevention. Caries is the result of
polymicrobial dysbiosis and not curable since the tooth structure is destroyed by fermentative acid
by-products from caries-associated bacterial species. Therefore, strong emphasis should be on
caries prevention. Caries risk assessment (CRA) is a widely accepted approach to caries
prevention, but has been criticized because it leads to patients with increased risk not being
identified. One drawback of CRA is that the polymicrobial nature of caries is not considered.
Furthermore, it lacks any molecular markers sampled directly at the tooth surface where caries
occurs. A key to improved CRA and prevention is a better understanding of molecular
mechanisms that promote oral commensals associated with general oral health. We have
identified an important trait of commensal oral streptococci that promotes molecular
commensalism: the pyruvate oxidase, SpxB, provides a growth advantage under aerobic
conditions since its metabolic activity generates additional ATP as well as pathogen-inhibiting
H2O2. SpxB therefore enables early commensal streptococci to outgrow and inhibit
H2O2 susceptible and caries-associated species. Our hypothesis is that commensal streptococci
producing higher amounts of metabolically important ATP and inhibitory H2O2 are more
competitive and thus allow dental plaque to be more resistant to cariogenic dysbiosis. We
therefore propose the following Specific Aims:
Aim 1: Cellular context - molecular mechanisms determining differential H2O2 production.
Aim 2: Oral context - determine whether spxB regulation influences competitiveness in vivo.
Aim 3: Clinical context - Real time measurements of H2O2 production and spxB expression
from ex vivo dental plaques.
The proposed aims will support our overall goal to better understand the health-associated traits
of oral commensals and lead to a paradigm shift in caries research towards that of molecular
commensalism; a vastly understudied area of oral microbiology. The gained
knowledge will provide important new insight into the development of new strategies to prevent
oral diseases like caries.

## Key facts

- **NIH application ID:** 10127620
- **Project number:** 5R01DE029492-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Jens Kreth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $500,980
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127620

## Citation

> US National Institutes of Health, RePORTER application 10127620, Pyruvate oxidase: a molecular determinant of commensalism among the oral microbiome (5R01DE029492-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10127620. Licensed CC0.

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