# Streptococcal secretion of pyruvate - a novel antioxidant strategy in the oral biofilm

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $192,500

## Abstract

Project Summary
Commensal streptococci play an important role in oral biofilm homeostasis. Disturbance of biofilm
homeostasis leads to dysbiosis and eventually disease development, including caries and
periodontal disease. Several oral streptococci are producing significant amounts of H2O2 able to
inhibit susceptible pathobionts involved in disease development. However, the production of H2O2
does not always correlate with the antagonistic ability of the producer. Our group recently
identified the mechanism behind this observation: oral streptococci secrete the central metabolite
pyruvate as potent H2O2 scavenger. The mechanism of pyruvate secretion as oxidative stress
response has been reported for eukaryotic cells, but has not been investigated in prokaryotes and
little is known about prokaryotic pyruvate transport in general. Our observation raises key
ecological questions about the role of commensal streptococci in the oral cavity: why do some
streptococcal H2O2 producers secrete protective amounts of pyruvate and others do not? What is
the genetic basis for this ability? What are the implications for oral health? The following specific
aims are proposed to identify and characterize the pyruvate secretion mechanism and its genetic
control in oral streptococci:
Aim I: Identify the pyruvate secretion mechanism and its specific regulation. We will identify
the genetic components required for pyruvate secretion by combining transposon mutagenesis
with an established genetic screening protocol. The regulation of these genes will be compared
between species. Aim I will determine how different streptococci modulate the H2O2/pyruvate
balance that is critical for oral microbial ecology.
Aim II: Characterize the regulatory network that determines the H2O2/pyruvate balance. We
will perform ChIP-seq (CCR+/-) under conditions of low and high pyruvate secretion to identify
the key regulatory components of this pathway. This will also serve as independent approach to
identify the pyruvate secretion mechanism.
An improved understanding of how the streptococcal community regulates its H2O2/pyruvate
balance will help to define the molecular determinates of disease development and provide a
novel target for disease prevention.

## Key facts

- **NIH application ID:** 10264935
- **Project number:** 5R21DE029612-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Jens Kreth
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $192,500
- **Award type:** 5
- **Project period:** 2020-09-16 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10264935

## Citation

> US National Institutes of Health, RePORTER application 10264935, Streptococcal secretion of pyruvate - a novel antioxidant strategy in the oral biofilm (5R21DE029612-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10264935. Licensed CC0.

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