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- W4366186281 abstract "An untapped therapeutic target for chronic wounds is the skin microbiota. Thus far, chronic wound treatments have focused on eliminating pathogenic microbes, such as Staphylococcus aureus, that are known to delay healing. However, it is not well understood how non-pathogenic bacterial colonization modulates wound healing, and if any colonizing bacteria confer a beneficial response. To initiate such an investigation, our lab performed culture-based and metagenomic analysis of non-infected diabetic foot ulcers. We identified a surprisingly prevalent wound inhabitant, Alcaligenes faecalis. Though detected in many chronic wounds, little is known about this species. We found that treating murine diabetic wounds with A. faecalis accelerates wound closure compared to control (p = 0.015). Furthermore, A. faecalis promotes diabetic keratinocyte migration in vitro and a 3-fold increase in proliferation in vivo. These keratinocyte behaviors are necessary for re-epithelialization, a critical step in early healing. Thus, the central goal of this study is to identify mechanisms by which A. faecalis mediates accelerated re-epithelialization. Towards this goal, we performed RNA-sequencing on A. faecalis-treated wounds. We discovered that A. faecalis reduces overexpression of matrix metalloproteinases (MMPs) during early healing. Overactivation of MMPs contributes to impaired re-epithelialization in diabetic healing. Furthermore, treating wounds with the pathogen S. aureus leads to delayed healing and increased MMP expression. We also found that protease sensitive, sterile supernatant of A. faecalis, rather than bacterial-cell surface molecules, promotes keratinocyte production of healing-associated cytokines. These results support a model wherein A. faecalis secretes a protein that improves re-epithelialization by balancing MMP expression. This work uncovers host mechanisms of bacterial-driven healing, as well as a microbial product capable of tuning the host wounding response." @default.
- W4366186281 created "2023-04-19" @default.
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- W4366186281 date "2023-05-01" @default.
- W4366186281 modified "2023-09-27" @default.
- W4366186281 title "1537 An understudied wound commensal bacterium accelerates diabetic wound healing by balancing matrix metalloproteinase overexpression" @default.
- W4366186281 doi "https://doi.org/10.1016/j.jid.2023.03.1554" @default.
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