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

J Allergy Clin Immunol. 2021 Mar;147(3):955-966.e16. doi: 10.1016/j.jaci.2020.06.024. Epub 2020 Jul 4.


Background: Staphylococcus aureus and Staphylococcus epidermidis are the most abundant bacteria found on the skin of patients with atopic dermatitis (AD). S aureus is known to exacerbate AD, whereas S epidermidis has been considered 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: The protease activity of S epidermidis isolates was compared with that of other staphylococcal species. The capacity of S epidermidis to degrade the barrier and induce inflammation was examined by 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 as EcpA, a cysteine protease under quorum sensing control. EcpA was shown to degrade desmoglein-1 and LL-37 in vitro, disrupt the physical barrier, and induce 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, Staphylococcus hominis, can inhibit EcpA production by S epidermidis.

Conclusion: S epidermidis has commonly been regarded as a beneficial skin microbe, whereas S aureus has been considered 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides / metabolism
  • Bacterial Proteins / metabolism*
  • Cathelicidins
  • Cells, Cultured
  • Cysteine Proteases / metabolism*
  • DNA, Bacterial / genetics
  • Dermatitis, Atopic / microbiology*
  • Dermatitis, Atopic / pathology
  • Desmoglein 1 / metabolism
  • Humans
  • Keratinocytes / microbiology
  • Keratinocytes / pathology
  • Mice
  • Mice, Inbred C57BL
  • Microbiota*
  • Severity of Illness Index
  • Skin / microbiology*
  • Skin / pathology
  • Staphylococcal Skin Infections / microbiology*
  • Staphylococcal Skin Infections / pathology
  • Staphylococcus epidermidis / enzymology*


  • Antimicrobial Cationic Peptides
  • Bacterial Proteins
  • DNA, Bacterial
  • Desmoglein 1
  • Cysteine Proteases
  • EcpA protein, Staphylococcus epidermidis
  • Cathelicidins