# Role of Clp proteins in pathophysiology of Streptococcus mutans

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2020 · $31,291

## Abstract

ABSTRACT
 Streptococcus mutans has been strongly implicated as the principal etiological agent in human
dental caries. It is also an important agent of infective endocarditis. S. mutans colonizes the oral
cavity through the formation of diverse, multispecies biofilms on the tooth surface, known as dental
plaque. S. mutans flourishes in the hostile environment of the oral cavity by responding efficiently
to various environmental fluxes, including severe nutrient limitation, fluctuations in pH and
temperature. Exposure of bacteria to these adverse environments can induce a stress tolerance
response through expression of a wide variety of proteins that provide cross-protection against
environmental challenges. The caseinolytic protease (Clp) family proteins, which contain
HSP100/Clp chaperones and the ClpP protease, constitute the core of bacterial protein quality
control systems involved in thermal and other stress responses. ClpP, a small cytoplasmic serine
protease, associates with a partner ATPase chaperone to form a functional complex that
specifically targets damaged or mis-folded proteins for degradation (collectively known as
regulated proteolysis) during stresses. While ClpP degrades the damaged protein, the ATPase
component determines the substrate specificity. Like other Firmicutes, streptococci encode five
Clp ATPases and only three of these (ClpC, ClpE, and ClpX) interact with ClpP to form active
complexes. ClpP is the primary intracellular protease that is required for stress tolerance
response, bacteriocin production, and biofilm formation among others While ClpX/P is the major
player, we recently found that ClpE/P is also involved in protein quality control in
streptococci. However, the molecular mechanism of substrate recognition and degradation by
ClpX/P and ClpE/P are not well understood in these organisms. In fact, very little is known about
protein quality control and their role in virulence in streptococci. Our long-term goal is to
understand the molecular mechanisms of regulated proteolysis in S. mutans and other oral
streptococci.

## Key facts

- **NIH application ID:** 10209781
- **Project number:** 3R01GM128241-03S1
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Indranil Biswas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,291
- **Award type:** 3
- **Project period:** 2018-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209781

## Citation

> US National Institutes of Health, RePORTER application 10209781, Role of Clp proteins in pathophysiology of Streptococcus mutans (3R01GM128241-03S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10209781. Licensed CC0.

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