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Activity of Staphylococcus epidermidis phenol-soluble modulin peptides expressed in Staphylococcus carnosus

Michael Otto1, D Shane O'Mahoney, Tina Guina

  • 1Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.

The Journal of Infectious Diseases
|July 24, 2004
PubMed

Insights

Researchers discovered a new peptide, phenol-soluble modulin delta (PSM delta), from Staphylococcus epidermidis. This peptide, along with others, stimulates macrophages and may contribute to staphylococcal sepsis.

Area of Science:

  • Microbiology
  • Immunology
  • Molecular Biology

Background:

  • Staphylococcus epidermidis produces phenol-soluble modulines (PSMs) that modulate host immune responses.
  • Previous studies identified three PSM peptides (alpha, beta, gamma), but their full contribution to staphylococcal activity is not completely understood.

Purpose of the Study:

  • To characterize a newly identified PSM peptide, designated PSM delta.
  • To investigate the immune-stimulating activities of PSM peptides.
  • To explore the role of PSM peptides in staphylococcal pathogenesis.

Main Methods:

  • Gene synthesis and expression of four PSM peptides (alpha, beta, gamma, delta) in Staphylococcus carnosus.
  • Purification and analysis of PSM peptides using liquid chromatography-mass spectrometry.
  • Assay of PSM peptide activity in activating the human immunodeficiency virus type 1 long-terminal repeat and inducing tumor necrosis factor-alpha production in THP-1 macrophages.

Main Results:

  • A novel 23-amino acid peptide, PSM delta (fMSIVSTIIEVVKTIVDIVKKFKK), was identified and synthesized.
  • Strains expressing individual PSM genes showed significantly enhanced PSM-like activity compared to the parent strain.
  • Purified PSM peptides, particularly in aggregated forms, activated the HIV-1 LTR and induced TNF-alpha production in macrophages.

Conclusions:

  • PSM peptides are key mediators of the modulin-like activity observed in staphylococci.
  • PSM delta represents a significant addition to the known family of staphylococcal PSMs.
  • These findings suggest a potential role for PSM peptides in the pathogenesis of severe staphylococcal sepsis.

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