title: Selective antimicrobial action is provided by phenol-soluble modulins derived from Staphylococcus epidermidis, a normal resident of the skin.
abstract: Antimicrobial peptides serve as a first line of innate immune defense against invading organisms such as bacteria and viruses. In this study, we hypothesized that peptides produced by a normal microbial resident of human skin, Staphylococcus epidermidis, might also act as an antimicrobial shield and contribute to normal defense at the epidermal interface. We show by circular dichroism and tryptophan spectroscopy that phenol-soluble modulins (PSMs) gamma and delta produced by S. epidermidis have an alpha-helical character and a strong lipid membrane interaction similar to mammalian AMPs such as LL-37. Both PSMs directly induced lipid vesicle leakage and exerted selective antimicrobial action against skin pathogens such as Staphylococcus aureus. PSMs functionally cooperated with each other and LL-37 to enhance antimicrobial action. Moreover, PSMs reduced Group A Streptococcus (GAS) but not the survival of S. epidermidis on mouse skin. Thus, these data suggest that the production of PSMgamma and PSMdelta by S. epidermidis can benefit cutaneous immune defense by selectively inhibiting the survival of skin pathogens while maintaining the normal skin microbiome.
authors.affiliation: Division of Dermatology, Department of Medicine, University of California San Diego, VA San Diego Health Care System, San Diego, California, USA.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Cogen
authors.forename: Kenshi
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Katheryn M
authors.initials: KM
authors.lastname: Sanchez
authors.forename: Robert A
authors.initials: RA
authors.lastname: Dorschner
authors.forename: Yuping
authors.initials: Y
authors.lastname: Lai
authors.forename: Daniel T
authors.initials: DT
authors.lastname: MacLeod
authors.forename: Justin W
authors.initials: JW
authors.lastname: Torpey
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.forename: Judy E
authors.initials: JE
authors.lastname: Kim
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D001427:Bacterial Toxins / Q000138:chemical synthesis / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D002942:Circular Dichroism; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology / Q000382:microbiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D008051:Lipid Bilayers / Q000378:metabolism; D008567:Membranes, Artificial; D051379:Mice; D008810:Mice, Inbred C57BL; D017433:Protein Structure, Secondary; D013207:Staphylococcal Skin Infections / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus; D013212:Staphylococcus epidermidis / Q000378:metabolism*; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D013297:Streptococcus pyogenes; D013559:Symbiosis
chemical_list: D023181:Antimicrobial Cationic Peptides; D001427:Bacterial Toxins; D008051:Lipid Bilayers; D008567:Membranes, Artificial; C025971:staphylococcal delta toxin