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Updated: Aug 23, 2026

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Regulated expression of pathogen-associated molecular pattern molecules in Staphylococcus epidermidis: quorum-sensing
Cuong Vuong1, Manuela Dürr, Aaron B Carmody
1Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, 903 S 4th Street, Hamilton, MT 59840, USA.
Abstract:
Phenol-soluble modulin (PSM) is a peptide complex produced by the nosocomial pathogen Staphylococcus epidermidis that has a strong capacity to activate the human innate immune response. We developed a novel method based on liquid chromatography-mass spectrometry (LC-MS) to quantify the production of the individual PSM components. Each PSM peptide was abundant in most of the 76 S epidermidis strains tested. Importantly, none of the PSM components were secreted by an agr mutant strain, indicating that PSM synthesis is regulated strictly by the agr quorum-sensing system. Furthermore, the agr mutant strain failed to elicit production of TNFalpha by human myeloid cells and induced significantly less neutrophil chemotaxis compared with the wild-type strain. Thus, quorum-sensing in S. epidermidis dramatically influenced activation of human host defence. We propose that an agr quorum-sensing mechanism facilitates growth and survival in infected hosts by adapting production of the pro-inflammatory PSMs to the stage of infection.
Insights
Staphylococcus epidermidis produces phenol-soluble modulin (PSM) peptides that activate the immune system. Their production is controlled by the agr quorum-sensing system, impacting host defense activation.
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Phenol-soluble modulin (PSM) peptides are produced by Staphylococcus epidermidis.
- PSMs activate the human innate immune response.
- The agr quorum-sensing system regulates bacterial virulence factors.
Purpose of the Study:
- To quantify individual PSM components produced by S. epidermidis.
- To investigate the role of the agr system in PSM production.
- To determine the impact of agr-regulated PSMs on host immune activation.
Main Methods:
- Development of a liquid chromatography-mass spectrometry (LC-MS) method for PSM quantification.
- Analysis of PSM production in 76 S. epidermidis strains.
- Assessment of TNF-alpha production by human myeloid cells.
- Measurement of neutrophil chemotaxis.
Main Results:
- Individual PSM peptides were abundant in most tested S. epidermidis strains.
- PSM production was strictly regulated by the agr quorum-sensing system.
- An agr mutant strain showed reduced TNF-alpha production and neutrophil chemotaxis.
Conclusions:
- The agr quorum-sensing system is critical for regulating PSM production in S. epidermidis.
- Agr-regulated PSMs play a significant role in activating human host defense mechanisms.
- Quorum-sensing facilitates S. epidermidis survival by modulating pro-inflammatory PSM production during infection.
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