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) γ and δ produced by S. epidermidis have an α-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 PSMγ and PSMδ by S. epidermidis can benefit cutaneous immune defense by selectively inhibiting the survival of skin pathogens while maintaining the normal skin microbiome.

Dermatophytic defensin with antiinfective potential

“…One such example is that P. aeruginosa in human skin produces compounds to kill and inhibit fungal growth (28). In addition, S. epidermidis was also found to generate phenol-soluble antimicrobial agents to contribute to normal defense at the epidermal interface (29). In this case, we assume that as common pathogens of animal and human skin (30), dermatophytes firstly need to fight against the bacterial flora by producing defensins to successfully survive on human skin.…”

Commensal skin bacteria as the probiotic of the cutaneous immune response

“…As mentioned previously, S. epidermidis is the most commonly isolated bacterial species from healthy human skin, and generally has a benign relationship with its host [6][7][8]. Despite its generally innocuous nature, over the past 20 years the research on S. epidermidis has been focused on its action as an opportunistic pathogen, and the identification of factors contributing to the conversion of S. epidermidis from a member of the resident microflora to an infectious agent.…”

“…S. epidermidis produces phenol soluble modulins g and d, lantibiotics and bacteriocins (such as epidermin, epilancin K7, epilancin 15X, Pep5 and staphylococcin 1580) [10] to inhibit the growth of S. aureus and group A Streptococcus (or S. pyogenes), thereby reducing the survival of group A Streptococcus, but not S. epidermidis, on skin [7]. By contrast, phenol soluble modulins from S. aureus have been labeled as virulence factors [11].…”

Transplantation of human skin microbiota in models of atopic dermatitis

“…The potential for Gram-positive commensal bacteria to influence AD has been suggested by recent findings that Staphylococcus epidermidis can activate TLR2, leading to increased production of antimicrobial peptides, tight-junction proteins, and vitamin D activation (13,38). Furthermore, S. epidermidis has been shown to produce several factors that can inhibit S. aureus growth and/or biofilm formation (41)(42)(43), suggesting an additional protective role for this commensal against the development of AD symptoms.…”