# Peptide Mediated Cell-Cell Communications in Streptococcus mutans

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2020 · $363,375

## Abstract

ABSTRACT:
Streptococcus mutans, an organism strongly associated with dental caries, utilizes a peptide-based cell density
dependent signaling system known as quorum-sensing (QS). This signaling pathway is responsible for
controlling major virulence traits such as bacteriocin production, biofilm formation, competence development,
and stress tolerance. In S. mutans, one of the peptides responsible for cell-cell communication is competence-
stimulating peptide (CSP). CSP acts as a signaling molecule to activate a two-component signal transduction
pathway called ComDE. CSP is synthesized inside the cell as a pre-peptide of 46-residues long, in which the
N-terminal 25-residue functions as a leader peptide. During secretion through a dedicated ABC transporter,
the leader peptide is cleaved and the matured 21-residue long peptide (CSP21) is concentrated in the milieu.
Our group was the first to identify the dedicated ABC transporter (NlmTE) necessary for CSP secretion. We
also discovered that CSP21 is further processed by a highly conserved cell-surface associated protease, which
we named SepM. We found that SepM cleaves CSP21 at the C-terminal end to create an 18-residue long
active signaling molecule (CSP18). When extracellular concentration of CSP18 reaches a critical density, the
ComD sensor kinase is activated by the peptide. The activated ComD then stimulates the ComE response
regulator and a variety of genes necessary for the observed phenotypic changes are induced by the activated
ComE. While the ComDE pathway is well studied at the phenotypic level, the molecular mechanisms by
which CSP activates this signaling pathway have not been evaluated. In this application we propose to study
the molecular mechanisms of CSP mediated cell-cell communication in S. mutans. Successful completion of
this study could shed light on the molecular basis for inhibition of S. mutans biofilm formation through
disruption of cell-cell communication.

## Key facts

- **NIH application ID:** 9979636
- **Project number:** 5R01DE026955-04
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** SASWATI BISWAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $363,375
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979636

## Citation

> US National Institutes of Health, RePORTER application 9979636, Peptide Mediated Cell-Cell Communications in Streptococcus mutans (5R01DE026955-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9979636. Licensed CC0.

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