{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:35:13Z","timestamp":1791725713523,"version":"4.3.4"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Maintaining a balanced skin microbiota is essential for preserving epidermal barrier integrity and overall skin health. Dysbiosis, particularly the opportunistic overgrowth of Staphylococcus aureus, is associated with barrier dysfunction and inflammatory dermatoses such as atopic dermatitis, psoriasis, and acne. In dysbiotic states, microbial regulatory mechanisms become disrupted, enabling pathogenic strains to proliferate and release proteases that degrade structural components of the skin barrier, increasing epidermal permeability in a manner analogous to \u2018leaky gut\u2019 physiopathology. Microbiota dysbiosis has further been proposed as an emerging hallmark of aging, contributing to chronic low-grade inflammation, impaired tissue repair, and progressive barrier decline. Current strategies predominantly target the microbiota itself, leaving the host tissue response to protease-mediated barrier disruption comparatively underaddressed. To fill this gap, an ex vivo human skin model was developed based on topical application of purified S. aureus serine protease SspA to skin explants, enabling controlled investigation of early host\u2013microbiota interaction events. Barrier function, junctional integrity, inflammatory mediators, and proteostasis were assessed through a panel of complementary biomarkers\u2014Lucifer Yellow permeability, claudin-1, desmoglein-1, filaggrin, IL-31, S100A8\/A9, PGE2, and protein carbonylation. SspA induced measurable barrier disruption, junctional protein loss, inflammatory mediator upregulation, and proteostasis impairment without overt tissue damage. A biotic culture filtrate of Bifidobacterium adolescentis partially attenuated SspA-induced protein carbonylation. This model provides the scientific community with a controlled, biologically relevant platform for identifying biomarkers of early barrier impairment and evaluating host-targeted interventions aimed at preventing or counteracting protease-driven barrier damage in dysbiosis-associated skin conditions. A better understanding of the early molecular mechanisms through which microbial virulence factors drive barrier disruption and proteostasis decline may further contribute to broader strategies aimed at preserving skin integrity during aging.<\/jats:p>","DOI":"10.3390\/microorganisms14061244","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T15:07:52Z","timestamp":1780326472000},"page":"1244","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["An Ex Vivo \u2018Leaky Skin\u2019 Model to Study Early Events Induced by Staphylococcus aureus Protease"],"prefix":"10.3390","volume":"14","author":[{"given":"Andrea","family":"Cavagnino","sequence":"first","affiliation":[{"name":"OxiProteomics, 2 Rue Antoine \u00c9tex, 94000 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Gouin","sequence":"additional","affiliation":[{"name":"OxiProteomics, 2 Rue Antoine \u00c9tex, 94000 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Breton","sequence":"additional","affiliation":[{"name":"CILIA Consulting, 20 Av. De Paris, 78000 Versailles, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5223-4226","authenticated-orcid":false,"given":"Martin","family":"Baraibar","sequence":"additional","affiliation":[{"name":"OxiProteomics, 2 Rue Antoine \u00c9tex, 94000 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nrmicro.2017.157","article-title":"The human skin microbiome","volume":"16","author":"Byrd","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.smim.2013.09.005","article-title":"Functions of the skin microbiota in health and disease","volume":"25","author":"Sanford","year":"2013","journal-title":"Semin. 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