{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:27:07Z","timestamp":1790882827698,"version":"4.1.0"},"reference-count":60,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T00:00:00Z","timestamp":1650844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["LP160100731"],"award-info":[{"award-number":["LP160100731"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1071822"],"award-info":[{"award-number":["APP1071822"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1059012"],"award-info":[{"award-number":["APP1059012"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Merchant foundation","award":["none"],"award-info":[{"award-number":["none"]}]},{"name":"Medical Research Futures Fund","award":["APP1137127"],"award-info":[{"award-number":["APP1137127"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Actinic keratosis (AK) is a premalignant lesion, common on severely photodamaged skin, that can progress over time to cutaneous squamous cell carcinoma (SCC). A high bacterial load of Staphylococcus aureus is associated with AK and SCC, but it is unknown whether this has a direct impact on skin cancer development. To determine whether S. aureus can have cancer-promoting effects on skin cells, we performed RNA sequencing and shotgun proteomics on primary human keratinocytes after challenge with sterile culture supernatant (\u2018secretome\u2019) from four S. aureus clinical strains isolated from AK and SCC. Secretomes of two of the S. aureus strains induced keratinocytes to overexpress biomarkers associated with skin carcinogenesis and upregulated the expression of enzymes linked to reduced skin barrier function. Further, these strains induced oxidative stress markers and all secretomes downregulated DNA repair mechanisms. Subsequent experiments on an expanded set of lesion-associated S. aureus strains confirmed that exposure to their secretomes led to increased oxidative stress and DNA damage in primary human keratinocytes. A significant correlation between the concentration of S. aureus phenol soluble modulin toxins in secretome and the secretome-induced level of oxidative stress and genotoxicity in keratinocytes was observed. Taken together, these data demonstrate that secreted compounds from lesion-associated clinical isolates of S. aureus can have cancer-promoting effects in keratinocytes that may be relevant to skin oncogenesis.<\/jats:p>","DOI":"10.3390\/cancers14092143","type":"journal-article","created":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T21:16:28Z","timestamp":1650921388000},"page":"2143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Skin Cancer-Associated S. aureus Strains Can Induce DNA Damage in Human Keratinocytes by Downregulating DNA Repair and Promoting Oxidative Stress"],"prefix":"10.3390","volume":"14","author":[{"given":"Annika","family":"Krueger","sequence":"first","affiliation":[{"name":"The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia"},{"name":"QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6507-5300","authenticated-orcid":false,"given":"Ahmed","family":"Mohamed","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathryn M.","family":"Kolka","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6275-3433","authenticated-orcid":false,"given":"Thomas","family":"Stoll","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4919-1448","authenticated-orcid":false,"given":"Julian","family":"Zaugg","sequence":"additional","affiliation":[{"name":"Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Linedale","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9257-9133","authenticated-orcid":false,"given":"Mark","family":"Morrison","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Peter","family":"Soyer","sequence":"additional","affiliation":[{"name":"Dermatology Research Centre, The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD 4102, Australia"},{"name":"Dermatology Department, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Hugenholtz","sequence":"additional","affiliation":[{"name":"Australian Centre for Ecogenomics, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8002-4680","authenticated-orcid":false,"given":"Ian H.","family":"Frazer","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1134-0951","authenticated-orcid":false,"given":"Michelle M.","family":"Hill","sequence":"additional","affiliation":[{"name":"The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia"},{"name":"QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia"},{"name":"The University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Herston, QLD 4006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1126\/science.aay9189","article-title":"The human tumor microbiome is composed of tumor type\u2013specific intracellular bacteria","volume":"368","author":"Nejman","year":"2020","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.trecan.2020.01.004","article-title":"The Cancer Microbiome: Distinguishing Direct and Indirect Effects Requires a Systemic View","volume":"6","author":"Xavier","year":"2020","journal-title":"Trends Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"326","DOI":"10.3322\/caac.21398","article-title":"The role of the microbiome in cancer development and therapy","volume":"67","author":"Bhatt","year":"2017","journal-title":"CA Cancer J. 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