# Gene Regulation and Physiology of Streptococcus mutans

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $362,188

## Abstract

PROJECT SUMMARY
Streptococcus mutans has the ability to catabolize a wide variety of sugars over a wide range of
concentrations, to store carbohydrates in different forms for catabolism during nutrient limitation, and to
adapt to the constant changes in carbohydrate source and availability in the oral cavity. Previous iterations
of DE12236 established the foundation for the present work using a two-pronged approach that involved in-
depth analysis of the regulation of expression of the fruA gene, which encodes an enzyme required for the
hydrolysis of homopolymers of fructose and has proven to be an ideal model to study substrate-dependent
induction and carbohydrate catabolite repression (CCR). Further, by studying a spectrum of sugar transport
and catabolism pathways, it was discovered that the molecular mechanisms in S. mutans for prioritization of
sugar utilization by preferred carbohydrate sources (i.e. CCR) deviate substantially from those of paradigm
organisms. We posit that the deviation of S. mutans from paradigms for CCR was driven by evolutionary
adaptations that have imparted to this organism the necessary degree of flexibility to respond to the wide
fluctuations in the amount and type of carbohydrates introduced into the human oral cavity. The present
proposal builds on these previous studies by focusing on two intimately intertwined behaviors. The first is a
detailed analysis of the molecular basis for persistent memory in the decision network for prioritizing the use
of preferred and non-preferred carbohydrate sources. The second focuses on the molecular mechanisms
and ecological basis for bistability in the response of populations of S. mutans to the presence of non-
preferred carbohydrates, such that under certain conditions only a sub-population of the cells in a community
produces the gene products needed for catabolism of non-preferred carbohydrates. Importantly, the sub-
population that activates the genes liberates substantial quantities of hexose into the environment, which can
be used by “cheaters” that do not activate the catabolic systems for the non-preferred carbohydrate. The fact
that abundant members of the microbiome engage in these behaviors has profound implications for the
dynamics of development, persistence and pathogenicity of oral biofilms. To understand the molecular basis
for, and ecological consequences of, these behaviors, we present two Specific Aims:
 Aim 1. Analyze the genetic basis for persistent memory in carbohydrate utilization and its
 contribution to fitness.
 Aim 2. Dissect the molecular basis and benefits of “cheating” behaviors in the catabolism of
 disaccharides in sub-populations of S. mutans.

## Key facts

- **NIH application ID:** 9912641
- **Project number:** 5R01DE012236-24
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Robert A Burne
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $362,188
- **Award type:** 5
- **Project period:** 1997-04-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912641

## Citation

> US National Institutes of Health, RePORTER application 9912641, Gene Regulation and Physiology of Streptococcus mutans (5R01DE012236-24). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9912641. Licensed CC0.

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