# Mechanisms of Pheromone-Controlled Lysozyme Resistance and Surface Display of Streptococcus pyogenes

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $399,750

## Abstract

Project Summary/Abstract
Little is understood about the physiological or regulatory factors of Streptococcus pyogenes that
enable switching between its commensal-like and virulent states. This proposal describes
experimental approaches that seek to continue defining and characterizing quorum-sensing
regulatory pathways that correspond to phenotypes consistent with the avirulent lifestyle of
Streptococcus pyogenes (Group A Streptococcus; GAS). The quorum sensing network in
Streptococcus pyogenes utilizing short hydrophobic peptide (SHP) pheromones and the pheromone
receptors Rgg2 and Rgg3 regulates several phenotypes, including biofilm development, cell
aggregation, aminoglycoside susceptibility, and lysozyme resistance, by an unknown mechanism.
Our studies indicate that each of these phenotypes depend upon the expression of a small protein of
unknown function. We hypothesize that this protein, referred to as StcB, is an inhibitor of an
enzyme(s) that targets peptidoglycan bonds of the cell wall. Additional studies indicate the target of
StcB is a murein hydrolase enzyme, called Isp, that contains cysteine and histidine-dependent
amidohydrolase/peptidase (CHAP) and acetylglucosaminidase domains. Governance of StcB and Isp
by the Rgg2/3 quorum sensing pathway accounts for significant changes to the bacterial cell surface,
resulting in differential attachment to fibronectin and epithelial cells, and differential immuno-
modulatory activities. This proposal seeks to elucidate the mechanisms by which StcB and Isp
enzymes account for biochemical changes to the surface of S. pyogenes, how these changes lead to
differential activity of surface structures and proteins, and how these changes affect the ability of S.
pyogenes to colonize the host and modulate immune activities.

## Key facts

- **NIH application ID:** 9814653
- **Project number:** 5R01AI091779-09
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** MICHAEL J FEDERLE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,750
- **Award type:** 5
- **Project period:** 2011-07-01 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9814653

## Citation

> US National Institutes of Health, RePORTER application 9814653, Mechanisms of Pheromone-Controlled Lysozyme Resistance and Surface Display of Streptococcus pyogenes (5R01AI091779-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9814653. Licensed CC0.

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