Staphylococcus epidermidis activates keratinocyte cytokine expression and promotes skin inflammation through the production of phenol-soluble modulins
Michael R. Williams,
Michelle D. Bagood,
Timothy J. Enroth,
Zoie L. Bunch,
Nina Jiang,
Edward Liu,
Samia Almoughrabie,
Shadi Khalil,
Fengwu Li,
Samantha Brinton,
Nadja B. Cech,
Alexander R. Horswill,
Richard L. Gallo
Affiliations
Michael R. Williams
Department of Dermatology, University of California, San Diego, San Diego, CA 92093, USA
Michelle D. Bagood
Department of Dermatology, University of California, San Diego, San Diego, CA 92093, USA
Timothy J. Enroth
Department of Veterans Affairs Denver Health Care System, Denver, CO, USA; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Zoie L. Bunch
Department of Chemistry and Biochemistry, University of North Carolina Greensboro, Greensboro, NC 27402, USA
Nina Jiang
Department of Dermatology, University of California, San Diego, San Diego, CA 92093, USA
Edward Liu
Department of Dermatology, University of California, San Diego, San Diego, CA 92093, USA
Samia Almoughrabie
Department of Dermatology, University of California, San Diego, San Diego, CA 92093, USA
Shadi Khalil
Department of Dermatology, University of California, San Diego, San Diego, CA 92093, USA
Fengwu Li
Department of Dermatology, University of California, San Diego, San Diego, CA 92093, USA
Samantha Brinton
Department of Dermatology, University of California, San Diego, San Diego, CA 92093, USA
Nadja B. Cech
Department of Chemistry and Biochemistry, University of North Carolina Greensboro, Greensboro, NC 27402, USA
Alexander R. Horswill
Department of Veterans Affairs Denver Health Care System, Denver, CO, USA; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Richard L. Gallo
Department of Dermatology, University of California, San Diego, San Diego, CA 92093, USA; Corresponding author
Summary: Staphylococcus epidermidis is a common microbe on human skin and has beneficial functions in the skin microbiome. However, under conditions of allergic inflammation, the abundance of S. epidermidis increases, establishing potential danger to the epidermis. To understand how this commensal may injure the host, we investigate phenol-soluble modulin (PSM) peptides produced by S. epidermidis that are similar to peptides produced by Staphylococcus aureus. Synthetic S. epidermidis PSMs induce expression of host defense genes and are cytotoxic to human keratinocytes. Deletion mutants of S. epidermidis lacking these gene products support these observations and further show that PSMs require the action of the EcpA bacterial protease to induce inflammation when applied on mouse skin with an intact stratum corneum. The expression of PSMδ from S. epidermidis is also found to correlate with disease severity in patients with atopic dermatitis. These observations show how S. epidermidis PSMs can promote skin inflammation.
