Staphylococcus epidermidis Antimicrobial δ-Toxin (Phenol-Soluble Modulin-γ) Cooperates with Host Antimicrobial Peptides to Kill Group A Streptococcus
| Autor: | Kenshi Yamasaki, Katheryn M. Sanchez, Richard L. Gallo, Laura E. Crotty Alexander, Jun Muto, Victor Nizet, Jackelyn Tanios, Judy E. Kim, Anna L. Cogen, Yuping Lai |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Neutrophils
Streptococcus pyogenes medicine.medical_treatment Antimicrobial peptides Bacterial Toxins lcsh:Medicine Dermatology medicine.disease_cause Cathelicidin Microbiology 03 medical and health sciences Mice Anti-Infective Agents Staphylococcus epidermidis medicine Animals Humans Immunoprecipitation lcsh:Science Pathogen Dermatology/Skin Infections 030304 developmental biology Skin 0303 health sciences Multidisciplinary Innate immune system biology 030306 microbiology Spectrum Analysis lcsh:R Microbiology/Medical Microbiology Neutrophil extracellular traps Antimicrobial biology.organism_classification Immunohistochemistry 3. Good health Mice Inbred C57BL lcsh:Q Peptides Research Article Protein Binding |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 1, p e8557 (2010) |
| ISSN: | 1932-6203 |
| Popis: | Antimicrobial peptides play an important role in host defense against pathogens. Recently, phenol-soluble modulins (PSMs) from Staphylococcus epidermidis (S. epidermidis) were shown to interact with lipid membranes, form complexes, and exert antimicrobial activity. Based on the abundance and innocuity of the cutaneous resident S. epidermidis, we hypothesized that their PSMs contribute to host defense. Here we show that S. epidermidis delta-toxin (PSMgamma) is normally present in the epidermis and sparsely in the dermis of human skin using immunohistochemistry. Synthetic delta-toxin interacted with neutrophil extracellular traps (NETs) and colocalized with cathelicidin while also inducing NET formation in human neutrophils. In antimicrobial assays against Group A Streptococcus (GAS), delta-toxin cooperated with CRAMP, hBD2, and hBD3. In whole blood, addition of delta-toxin exerted a bacteriostatic effect on GAS, and in NETs, delta-toxin increased their killing capacity against this pathogen. Coimmunoprecipitation and tryptophan spectroscopy demonstrated direct binding of delta-toxin to host antimicrobial peptides LL-37, CRAMP, hBD2, and hBD3. Finally, in a mouse wound model, GAS survival was reduced (along with Mip-2 cytokine levels) when the wounds were pretreated with delta-toxin. Thus, these data suggest that S. epidermidis-derived delta-toxin cooperates with the host-derived antimicrobial peptides in the innate immune system to reduce survival of an important human bacterial pathogen. |
| Databáze: | OpenAIRE |
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