Staphylococcus epidermidis protease EcpA can be a deleterious component of the skin microbiome in atopic dermatitis

Background: S. aureus and S. epidermidis are the most abundant bacteria found on the skin of patients with atopic dermatitis (AD). S. aureus is known to exacerbate AD while S. epidermidis was considered as a beneficial commensal organism.

Objective: In this study, we hypothesized that S. epidermidis could promote skin damage in AD by the production of a protease that damages the epidermal barrier.

Methods: Protease activity of S. epidermidis isolates was compared with other staphylococcal species. The capacity of S. epidermidis to degrade the barrier and induce inflammation was examined using human keratinocyte tissue culture and mouse models. Skin swabs from atopic and healthy adult subjects were analyzed for the presence of S. epidermidis genomic DNA and mRNA.

Results: S. epidermidis strains were observed to produce strong cysteine protease activity when grown at high density. The enzyme responsible for this activity was identified to be EcpA, a cysteine protease under quorum sensing control. EcpA was shown to degrade desmoglein-1 and LL-37 in vitro and disrupted the physical barrier and induced skin inflammation in mice. The abundance of S. epidermidis and expression of ecpA mRNA were increased on the skin of some patients with AD and this correlated with disease severity. Another commensal skin bacterial species, S. hominis, can inhibit EcpA production by S. epidermidis.

Conclusion: S. epidermidis was commonly regarded as a beneficial skin microbe while S. aureus considered to be deleterious. This study suggests that the overabundance of S. epidermidis found on some atopic patients can act similarly to S. aureus and damage the skin by expression of a cysteine protease.

Keywords: Atopic dermatitis; Staphylococcus epidermidis; cytokine; dysbiosis; epidermal barrier; inflammation; microbiome; protease; skin.