1537 An understudied wound commensal bacterium accelerates diabetic wound healing by balancing matrix metalloproteinase overexpression

An untapped therapeutic target for chronic wounds is the skin microbiota. Thus far, wound treatments have focused on eliminating pathogenic microbes, such as Staphylococcus aureus, that are known to delay healing. However, it not well understood how non-pathogenic bacterial colonization modulates healing, and if any colonizing bacteria confer a beneficial response. To initiate an investigation, our lab performed culture-based metagenomic analysis of non-infected diabetic foot ulcers. We identified surprisingly prevalent inhabitant, Alcaligenes faecalis. Though detected in many wounds, little about this species. found treating murine with A. faecalis accelerates closure compared control (p = 0.015). Furthermore, promotes keratinocyte migration vitro 3-fold increase proliferation vivo. These behaviors necessary re-epithelialization, critical step early Thus, central goal study identify mechanisms by which mediates accelerated re-epithelialization. Towards goal, we RNA-sequencing faecalis-treated wounds. discovered reduces overexpression matrix metalloproteinases (MMPs) during Overactivation MMPs contributes impaired re-epithelialization pathogen S. aureus leads delayed healing increased MMP expression. also protease sensitive, sterile supernatant faecalis, rather than bacterial-cell surface molecules, production healing-associated cytokines. results support model wherein secretes protein improves balancing This work uncovers host bacterial-driven microbial product capable tuning wounding