Gene expression profile at single cell level from untreated and Enterococcus faecalis-infected skin wounds

Enterococcus faecalis (E. faecalis) is a Gram-(+) opportunistic pathogen associated with predominantly nosocomial wound infections. E. faecalis has been shown to suppress or evade immune-mediated clearance by the immune system and promote persistent infection. Here, we sought to interrogate whether E. faecalis infection induces transcriptomic changes in the host at the single-cell resolution using a mouse excisional wound model. Keratinocyte, fibroblast, endothelial and immune cell populations reveal unique clusters in the infected wounds. Cell communication analysis discovered strong ligand-receptor interactions between macrophages and endothelial cells in the infected niche, whilst fibroblast and keratinocytes instruct healing cellular interactions in untreated skin wounds. We also identified differential terminal lineage driving genes, following RNA velocity in each condition. Together, results suggest that E. faecalis infection alters the skin transcriptome, which may help promote the chronicity of bacteria-infected wounds. Overall design: A single, 6-mm full-thickness wound was created on the shaven dorsal skin of C57BL/6J mice. The wounds were inoculated with Enterococcus faecalis and all wounds were covered with Tegaderm. Tissues were harvested at day 4 with a 6-mm biopys punch with minimal adjacent healthy tissue.