# Role of Lrg pyruvate uptake system in Streptococcus mutans environmental adaptation

> **NIH NIH R56** · UNIVERSITY OF FLORIDA · 2022 · $362,188

## Abstract

The ability of Streptococcus mutans to efficiently and rapidly adjust to the changing environment is an
essential element of the persistence and cariogenicity of the organism. During the previous funding
period of our R01 grant, we revealed that the S. mutans LrgAB system, hypothesized to mediate cell
death and lysis with its partner proteins CidAB, functions as a stationary-phase pyruvate uptake system
and its activity is tightly regulated in response to both the bacteria’s extracellular and intracellular
metabolic status. Pyruvate directs key metabolic fluxes for growth and energy generation, and is rapidly
recycled into the cell upon nutrient limitation as an overflow metabolite. The population distribution of
lrgAB expression at stationary phase also takes on a bimodal character, suggesting that pyruvate
uptake may be limited to a lrgAB-expressing subpopulation of stationary phase cells. Therefore, this
renewal proposal tests the hypothesis that pyruvate may initiate a cellular and/or metabolic response
through LrgAB to deal with unfavorable conditions, consequently providing a selective advantage to a
subpopulation of cells to overcome the limited resources and environmental fluctuations, experienced in
the oral cavity, consequently promoting the resilience of a biofilm community. This hypothesis will be
tested by dissecting the response of S. mutans to key environmental parameters such as external
pyruvate and oxygen, critical for lrgAB expression and function, in the context of underlying
biochemical, transcriptomic, and metabolomic processes. The fact that diverse members of the
microbiome engage in the response of lrg to environmental cues also has profound implications for the
effect of microbially dynamic environments in lrg-mediated phenotypes. Study of the contribution of the
Lrg system to the integration of complex environmental signals into the regulatory networks modulating
S. mutans virulence and homeostasis will be undertaken as described in the following aims: Aim 1
addresses the metabolic coordination by lrgAB expression and in response to key environmental
components, external pyruvate and oxygen, in the context of bacterial community and during growth
phase transitions (targeted metabolomics and transcriptomics). Given that the dynamic regulation of
pyruvate uptake is primarily driven by Plrg activation, Aim 2 addresses how the lrgAB promoter is
differentially activated in response to the cell’s external- and internal metabolic status. For this, we
examine the potential interplays among CcpA, CodY, and LytT on the lrgAB promoter, and the process
by which LytST senses external pyruvate and subsequently activates the lrgAB promoter. And Aim 3
tests the hypothesis that taxonomic composition and their metabolic activity may shape local
environment, and have an effect on the pyruvate-mediated community development of S. mutans in
oral cavity, by using an ex vivo saliva biofilm model containing oral commensal bacteria.

## Key facts

- **NIH application ID:** 10645783
- **Project number:** 2R56DE025237-06A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Sang-Joon Ahn
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $362,188
- **Award type:** 2
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10645783

## Citation

> US National Institutes of Health, RePORTER application 10645783, Role of Lrg pyruvate uptake system in Streptococcus mutans environmental adaptation (2R56DE025237-06A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10645783. Licensed CC0.

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