# Quorum sensing, diversity and skin inflammation

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2022 · $595,187

## Abstract

Project Summary
The surface of the skin is persistently colonized with a community of bacteria that includes numerous different
species and strains of coagulase negative staphylococci (CoNS). There is mounting evidence that these CoNS
prevent colonization of the skin by pathogens such Staphylococcus aureus, thereby protecting the skin from
damage. Our central hypothesis is that CoNS on the skin use a peptide quorum-sensing system to limit S.
aureus-induced damage to the host. All Staphylococci have a quorum-sensing system, which is also called the
accessory gene regulator (agr). The agr system responds to a secreted peptide signal (autoinducing peptide or
AIP), and this system controls expression of toxins and exo-enzymes from S. aureus. In CoNS, the function of
the agr system is less clear, but our recent data suggest CoNS uses the agr system to survive on the skin,
establish diversity, and compete against S. aureus. In support of this hypothesis, we have discovered that several
common skin CoNS species produce AIP signals that inhibit the S. aureus agr system and limit skin damage.
However, strain-specific knowledge of the genetic basis for this hypothesis is essential since not all CoNS strains
are benefical and some can trigger inflammation. To better understand these mechanisms and their significance
to human skin immune defense, in Aim 1 we will investigate whether CoNS AIP signals prevent skin damage by
S. aureus. To carry out this aim, we will identify the AIP structures from culture media of selected skin CoNS
strains, and test their activity as S. aureus agr inhibitors in vitro and in skin models of deep tissue infection and
superficial colonization that drives skin inflammation. We will also compare CoNS and S. aureus polymicrobial
interactions on the skin using explants and animal models, and assess the contribution of CoNS agr function to
antimicrobial peptide production and mixed infection with S. aureus. In Aim 2, we propose that dysregulation of
agr-regulated factors is a major mechanism that influences skin disease. Our preliminary studies indicate that
high expression of the S. epidermidis EcpA protease promotes epidermal damage and subsequent inflammation.
We will investigate S. epidermidis EcpA protease expression and the host target(s) of cleavage, and we will
compare WT and mutant strains to define the impact on skin barrier disruption and inflammation. We will also
investigate protective CoNS species that use AIPs to inhibit S. epidermidis EcpA production. Defining deleterious
mechanisms will enable better understanding of factors favoring survival of beneficial vs harmful CoNS. In Aim
3, we will determine how CoNS use agr-regulated factors to survive on the skin. Based on our preliminary studies
with S. epidermidis, we hypothesize that CoNS strains colonize the skin using the agr quorum-sensing system.
We will assess the requirement of various agr-regulated loci for CoNS survival on skin and evaluate the function
of identi...

## Key facts

- **NIH application ID:** 10411990
- **Project number:** 5R01AI153185-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Richard L Gallo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $595,187
- **Award type:** 5
- **Project period:** 2020-06-12 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10411990

## Citation

> US National Institutes of Health, RePORTER application 10411990, Quorum sensing, diversity and skin inflammation (5R01AI153185-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10411990. Licensed CC0.

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