# Biosynthesis, structure and function of cell wall in Streptococcus mutans

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2020 · $350,313

## Abstract

The cell wall of many species of Lactobacillales consists of multiple peptidoglycan layers
decorated with serotype-specific polysaccharides that are characterized by the presence of
rhamnose. Streptococcus mutans is a key etiological agent of human dental caries, and has
also been implicated in bacteremia and infective endocarditis. Based on the chemical structures
of serotype-specific carbohydrates, S. mutans is classified into serotypes c, e, f and k with
approximately 70-80% of strains found in the oral cavity classified as serotype c. The serotype
c-specific carbohydrate (SCC) of S. mutans is composed of a polyrhamnose backbone with α-
linked glucose side-chains. Although carbohydrate structures have been reported for all
S. mutans serotypes, our recent insights into the structure of these glycopolymers indicate that
the functionally important modification, glycerol phosphate, was overlooked, possibly due to its
loss during the purification steps. This new finding justifies a re-examination of the chemical
structures of serotype-specific carbohydrates. One of the goals of the proposed study is to
determine the molecular structure of SCC isolated from S. mutans using mild, non-destructive
methods. Moreover, little is known about the multienzyme processes involved in attachment of
the glucose side-chains to the polyrhamnose backbone of SCC and the function of the glycerol
phosphate modification in S. mutans. Our preliminary findings revealed that the glycerol
phosphate modification plays important roles in S. mutans morphology, autolysis, resistance to
antimicrobials and biofilm formation. We propose to identify and functionally characterize the
enzymes involved in glucose side-chain attachment to polyrhamnose, and investigate the
molecular mechanisms underlying the functions of glycerol phosphate modification in
morphology, autolysis and biofilm formation. To accomplish our goals, we will employ
streptococcal genetics, in vitro enzymology, NMR spectroscopy of polysaccharides, analytical
chemistry, mass spectrometric analysis of phospholipids, and various methods of microscopy
including AFM-based nanomechanics. The cell wall biosynthetic machinery is an historically
preferred target for the development of novel antimicrobials. In order to validate the pathway of
SCC decoration with glycerol phosphate as a potential drug target, we will determine the role of
this modification in a rat caries model. Successful outcomes will guide future studies of cell wall
biogenesis in other important Gram-positive bacteria and the development of novel strategies to
treat S. mutans infections.

## Key facts

- **NIH application ID:** 9973591
- **Project number:** 1R01DE028916-01A1
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Natalia Korotkova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $350,313
- **Award type:** 1
- **Project period:** 2020-04-08 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973591

## Citation

> US National Institutes of Health, RePORTER application 9973591, Biosynthesis, structure and function of cell wall in Streptococcus mutans (1R01DE028916-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9973591. Licensed CC0.

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