Selective antimicrobial action is provided by phenol-soluble modulins derived from Staphylococcus epidermidis, a normal resident of the skin.
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.
Cogen
Anna L
AL
Division of Dermatology, Department of Medicine, University of California San Diego, VA San Diego Health Care System, San Diego, California, USA.
Yamasaki
Kenshi
K
Sanchez
Katheryn M
KM
Dorschner
Robert A
RA
Lai
Yuping
Y
MacLeod
Daniel T
DT
Torpey
Justin W
JW
Otto
Michael
M
Nizet
Victor
V
Kim
Judy E
JE
Gallo
Richard L
RL
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
D023181:Antimicrobial Cationic Peptides; D001427:Bacterial Toxins; D008051:Lipid Bilayers; D008567:Membranes, Artificial; C025971:staphylococcal delta toxin