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Updated: May 26, 2026

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Distribution and regulation of the mobile genetic element-encoded phenol-soluble modulin PSM-mec in
Som S Chatterjee1, Liang Chen, Hwang-Soo Joo
1Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, Maryland, United States of America.
Abstract:
The phenol-soluble modulin PSM-mec is the only known staphylococcal toxin that is encoded on a mobile antibiotic resistance determinant, namely the staphylococcal cassette chromosome (SCC) element mec encoding resistance to methicillin. Here we show that the psm-mec gene is found frequently among methicillin-resistant Staphylococcus aureus (MRSA) strains of SCCmec types II, III, and VIII, and is a conserved part of the class A mec gene complex. Controlled expression of AgrA versus RNAIII in agr mutants of all 3 psm-mec-positive SCCmec types demonstrated that expression of psm-mec, which is highly variable, is controlled by AgrA in an RNAIII-independent manner. Furthermore, psm-mec isogenic deletion mutants showed only minor changes in PSMα peptide production and unchanged (or, as previously described, diminished) virulence compared to the corresponding wild-type strains in a mouse model of skin infection. This indicates that the recently reported regulatory impact of the psm-mec locus on MRSA virulence, which is opposite to that of the PSM-mec peptide and likely mediated by a regulatory RNA, is minor when analyzed in the original strain background. Our study gives new insight in the distribution, regulation, and role in virulence of the PSM-mec peptide and the psm-mec gene locus.
Insights
The phenol-soluble modulin PSM-mec toxin is frequently found in methicillin-resistant Staphylococcus aureus (MRSA). Its expression is controlled by AgrA, and it has a minor impact on MRSA virulence.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Phenol-soluble modulin PSM-mec is a unique staphylococcal toxin encoded on the mobile antibiotic resistance determinant, the staphylococcal cassette chromosome (SCC) element mec.
- This element confers methicillin resistance in Staphylococcus aureus.
Purpose of the Study:
- To investigate the distribution, regulation, and virulence role of the PSM-mec peptide and its gene locus in MRSA.
- To clarify the regulatory mechanisms controlling psm-mec expression and its impact on MRSA pathogenesis.
Main Methods:
- Analysis of psm-mec gene distribution in MRSA strains of SCCmec types II, III, and VIII.
- Controlled expression studies in agr mutants to determine regulation by AgrA and RNAIII.
- Construction and analysis of psm-mec isogenic deletion mutants in a mouse model of skin infection.
Main Results:
- The psm-mec gene is frequently found in MRSA strains with SCCmec types II, III, and VIII, forming a conserved part of the class A mec gene complex.
- PSM-mec expression is controlled by AgrA independently of RNAIII and shows high variability.
- psm-mec deletion mutants exhibited minor changes in PSMα peptide production and virulence compared to wild-type strains.
Conclusions:
- PSM-mec is a conserved component in specific MRSA SCCmec types, regulated by AgrA.
- The PSM-mec peptide's direct contribution to MRSA virulence appears minor, with its regulatory RNA impact being limited in the original strain background.
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