1518 Identification of gene products from staphylococcus aureus that inhibit keratinocyte migration and wound repair

Staphylococcus aureus is a major human pathogen that can complicate wound repair, leading to delayed healing and risk of invasive infection. To better understand how this bacterium impairs we employed bacterial genetic approach with combination unbiased transcriptomic analysis andin vitro in vivo models epithelial repair. Compared an intact layer normal keratinocytes (NHEK), RNA sequencing revealed wounded monolayer was uniquely susceptible S. aureus. This response occurred during low dose exposure sterile conditioned media also vitroclosure scratch wounds (p < 0.0001) without significant increase cell permeability or cytotoxicity. Similarly, splinted full-thickness mouse skin wild-type live (USA300) reepithelialization closure = 0.008). However, neither these exhibited after similar amounts commensal Staphylococcus, such as hominis, targeted mutant strain (USA300Δagr) deficient quorum sensing. These observations lead us investigate what specific gene products sensing harm migrating keratinocytes. Targeted deletion virulence factors under control showed loss PSMα operon specifically compromised keratinocyte migration 0.0001), but other the PSMβ operon, 10 proteases, hld, hla did not restore migration. Ongoing transcriptional proteomic underway further damages compared skin. We propose targeting may improve help infected by antibiotic resistant strains