Host response of human epidermis to Methicillin-resistant Staphylococcus aureus biofilm infection and synthetic antibiofilm peptide treatment

Bacterial biofilm infections associated with wounded skin are prevalent, recalcitrant and in urgent need of treatments. Additionally, host responses in the skin to biofilm infections are not well understood. Here we employed a human organoid skin model to explore the transcriptomic changes of thermally-injured epidermis to Methicillin-resistant Staphylococcus aureus (MRSA) biofilm colonization. MRSA biofilm impaired skin barrier function, enhanced extracellular matrix remodelling, elicited inflammatory responses including IL-17, IL-12 family and IL-6 family interleukin signalling and modulated skin metabolism. Synthetic antibiofilm peptide DJK-5 effectively diminished MRSA biofilm associated with wounded human ex vivo skin. In the epidermis, DJK-5 shifted the overall skin transcriptome towards homeostasis including modulating the biofilm induced inflammatory response, promoting the skin DNA repair function, and downregulating MRSA invasion of thermally damaged skin. These data revealed the intrinsic promise of synthetic peptides in treating inflammation and biofilm infections. Overall design: Samples are RNA-Seq libraries, based on a human skin organoid model of burn wounds, bacterial infection, and treatment with synthetic peptides. Included sample types are: untreated skin (control); burned skin; burned skin + MRSA infection; and burned skin + MRSA infection + peptide treatment