# Peptide Autoinducers of Staphylococcal Pathogenicity

> **NIH NIH R01** · PRINCETON UNIVERSITY · 2021 · $521,659

## Abstract

A research program will be undertaken to study agr signal transduction in the commensal pathogen,
Staphylococcus aureus. The accessory gene regulator (agr) locus found in all staphylococci encodes a quorum
sensing (QS) circuit that controls the expression of virulence and other accessory genes. It consists of two
oppositely oriented transcriptional units, of which one encodes four proteins, AgrBDCA, involved in production
and sensing of an autoinducer peptide (AIP), and the other encodes a regulatory RNA that is the effector of
target gene regulation. The finding that staphylococcal virulence can be inhibited through antagonism of this
QS pathway has fueled tremendous interest in understanding the detailed mechanisms at play throughout the
circuit. Building on recent breakthroughs that have allowed us to reconstitute much as the quorum sensing
circuit using purified components, we propose to integrate chemical, biochemical, biophysical and genetic tools
for the purpose of obtaining a deeper understanding into the molecular processes underlying the production
and sensing of the autoinducer peptide (AIP) pheromone that is central to agr regulation. The program will
move forward in three directions: Aim 1, identifying the key missing players in AIP biosynthesis; Aim 2,
understanding how agonism and antagonism of the QS system relates to newly discovered conformational
changes in the AIP receptor, AgrC, and; Aim 3, identifying novel modulators of agr through sophisticated
target-based screens. These studies will lay the groundwork for the development of therapeutic strategies
targeting agr, but also contribute to a fundamental understanding of QS systems of this type, which are
pervasive in the low-GC bacterial phylum, Firmicutes.

## Key facts

- **NIH application ID:** 10086365
- **Project number:** 5R01AI042783-20
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Tom Muir
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $521,659
- **Award type:** 5
- **Project period:** 1998-05-15 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10086365

## Citation

> US National Institutes of Health, RePORTER application 10086365, Peptide Autoinducers of Staphylococcal Pathogenicity (5R01AI042783-20). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10086365. Licensed CC0.

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