{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T18:06:43Z","timestamp":1792260403481,"version":"4.4.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Squamous cell carcinoma (SCC) is a common type of skin cancer that typically arises from premalignant precursor lesions named actinic keratoses (AK). Chronic inflammation is a well-known promoter of skin cancer progression. AK and SCC have been associated with an overabundance of the bacterium <jats:italic>Staphylococcus aureus<\/jats:italic> (<jats:italic>S. aureus<\/jats:italic>). Certain secreted products from <jats:italic>S. aureus<\/jats:italic> are known to promote cutaneous pro-inflammatory responses; however, not all <jats:italic>S. aureus<\/jats:italic> strains produce these. As inflammation plays a key role in SCC development, we investigated the pro-inflammatory potential and toxin secretion profiles of skin-cancer associated <jats:italic>S. aureus<\/jats:italic>. Sterile culture supernatants (\u201csecretomes\u201d) of <jats:italic>S. aureus<\/jats:italic> clinical strains isolated from AK and SCC were applied to human keratinocytes <jats:italic>in vitro.<\/jats:italic> Some <jats:italic>S. aureus<\/jats:italic> secretomes induced keratinocytes to overexpress inflammatory mediators that have been linked to skin carcinogenesis, including IL-6, IL-8, and TNF\u03b1. A large phenotypic variation between the tested clinical strains was observed. Strains that are highly pro-inflammatory <jats:italic>in vitro<\/jats:italic> also caused more pronounced skin inflammation in mice. Proteomic characterization of <jats:italic>S. aureus<\/jats:italic> secretomes using mass spectrometry established that specific <jats:italic>S. aureus<\/jats:italic> enzymes and cytolytic toxins, including hemolysins, phenol-soluble modulins, and serine proteases, as well as currently uncharacterized proteins, correlate with the pro-inflammatory <jats:italic>S. aureus<\/jats:italic> phenotype. This study is the first to describe the toxin secretion profiles of AK and SCC-associated <jats:italic>S. aureus<\/jats:italic>, and their potential to induce a pro-inflammatory environment in the skin. Further studies are needed to establish whether these <jats:italic>S. aureus<\/jats:italic> products promote SCC development by mediating chronic inflammation.<\/jats:p>","DOI":"10.3389\/fmicb.2021.789042","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T08:10:36Z","timestamp":1643098236000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["Secreted Toxins From Staphylococcus aureus Strains Isolated From Keratinocyte Skin Cancers Mediate Pro-tumorigenic Inflammatory Responses in the Skin"],"prefix":"10.3389","volume":"12","author":[{"given":"Annika","family":"Krueger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Zaugg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Chisholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Linedale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Lachner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siok Min","family":"Teoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zewen K.","family":"Tuong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel W.","family":"Lukowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Morrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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