Skin cancer-associated S. aureus downregulates DNA repair mechanisms, and promotes oxidative stress and DNA damage in human keratinocytes
Krueger A, Mohamed A, Kolka CM, Stoll T, Zaugg J, Linedale R, Morrison M, Soyer HP, Hugenholtz P, Frazer IH, Hill MM. Skin Cancer-Associated S. aureus
Strains Can Induce DNA Damage in Human Keratinocytes by Downregulating DNA Repair and Promoting Oxidative Stress. Cancers (Basel). 2022 Apr 25;14(9):2143. doi: 10.3390/cancers14092143. PMID: 35565272.
- Organism: Staphylococcus capitis, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus
- Instrument: 6470A Triple Quadrupole LC/MS
Skin, S. aureus secretome, multiomics, actinic keratosis, squamous cell carcinoma, DNA damage
Lab head: Michelle Hill
Submitter: Thomas Stoll
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.
Created on 2/14/22, 10:13 PM