Dataset Information

Skin cancer-associated S. aureus downregulates DNA repair mechanisms, and promotes oxidative stress and DNA damage in human keratinocytes

ABSTRACT: Actinic keratoses (AK) are premalignant lesions common on photo-damaged skin that, over time, can progress to 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 is able to trigger pro-tumorigenic skin responses, we performed RNAseq and shotgun proteomics on primary human keratinocytes after challenge with sterile culture supernatant (‘secretome’) from S. aureus clinical strains isolated from AK and SCC. Certain S. aureus secretomes induced keratinocytes to overexpress SCC biomarkers that have been associated with skin carcinogenesis, and upregulate the expression of enzymes linked with reduced skin barrier function. Further, S. aureus secretomes downregulated DNA repair mechanisms and induced oxidative stress markers. Subsequent experiments confirmed that exposure to SCC-derived S. aureus secretomes lead to increased intracellular ROS levels and DNA damage in primary human keratinocytes. Altogether, this study reveal a novel mechanism for the pro-tumorigenic activity of S. aureus. Further studies are required to determine whether S. aureus products promote SCC development in vivo, which would have important implications for the treatment of AK and prevention of SCC.

ORGANISM(S): Staphylococcus Capitis Staphylococcus Aureus Staphylococcus Epidermidis Staphylococcus

SUBMITTER: Thomas Stoll

PROVIDER: PXD031676 | panorama | Tue May 17 00:00:00 BST 2022

REPOSITORIES: PanoramaPublic

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Publications

Skin Cancer-Associated S. aureus Strains Can Induce DNA Damage in Human Keratinocytes by Downregulating DNA Repair and Promoting Oxidative Stress.

Krueger Annika A Mohamed Ahmed A Kolka Cathryn M CM Stoll Thomas T Zaugg Julian J Linedale Richard R Morrison Mark M Soyer H Peter HP Hugenholtz Philip P Frazer Ian H IH Hill Michelle M MM

Cancers 20220425 9

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 ch ...[more]

PMID: 35565272

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Dataset Information

Skin cancer-associated S. aureus downregulates DNA repair mechanisms, and promotes oxidative stress and DNA damage in human keratinocytes

Publications

Skin Cancer-Associated <i>S. aureus</i> Strains Can Induce DNA Damage in Human Keratinocytes by Downregulating DNA Repair and Promoting Oxidative Stress.

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