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Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells
09:25

Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells

Published on: August 19, 2016

Staphylococcus epidermidis antimicrobial delta-toxin (phenol-soluble modulin-gamma) cooperates with host

Anna L Cogen1, Kenshi Yamasaki, Jun Muto

  • 1Division of Dermatology, University of California San Diego, San Diego, California, United States of America.

Plos One
|January 7, 2010
PubMed

Insights

Staphylococcus epidermidis delta-toxin, a skin peptide, enhances innate immunity by working with host antimicrobial peptides. This cooperation boosts the immune system's ability to fight Group A Streptococcus infections.

Area of Science:

  • Microbiology
  • Immunology
  • Dermatology

Background:

  • Antimicrobial peptides are crucial for host defense against pathogens.
  • Phenol-soluble modulins (PSMs) from Staphylococcus epidermidis exhibit antimicrobial activity.
  • S. epidermidis is abundant and generally harmless on human skin, suggesting its PSMs may aid host defense.

Purpose of the Study:

  • To investigate the role of S. epidermidis delta-toxin (PSMgamma) in host defense against bacterial pathogens.
  • To determine if delta-toxin interacts with host immune components and enhances antimicrobial activity.

Main Methods:

  • Immunohistochemistry to detect delta-toxin in human skin.
  • In vitro assays using synthetic delta-toxin with human neutrophils, neutrophil extracellular traps (NETs), and various antimicrobial peptides.
  • Antimicrobial assays against Group A Streptococcus (GAS) in whole blood and NETs.
  • Biochemical methods (coimmunoprecipitation, tryptophan spectroscopy) to confirm direct binding.
  • A mouse wound model to assess in vivo efficacy.

Main Results:

  • Delta-toxin was detected in human epidermis and dermis.
  • Synthetic delta-toxin interacted with NETs, colocalized with cathelicidin, and induced NET formation.
  • Delta-toxin showed synergistic antimicrobial effects with host peptides (CRAMP, hBD2, hBD3) against GAS.
  • It exerted a bacteriostatic effect on GAS in whole blood and enhanced NET-mediated killing.
  • Direct binding of delta-toxin to host antimicrobial peptides (LL-37, CRAMP, hBD2, hBD3) was confirmed.
  • In a mouse wound model, delta-toxin pretreatment reduced GAS survival and Mip-2 levels.

Conclusions:

  • S. epidermidis delta-toxin is a component of the skin's innate immune system.
  • Delta-toxin cooperates with host antimicrobial peptides to combat bacterial infections like GAS.
  • This interaction enhances the host's defense mechanisms against pathogens.

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