Wound microbiota-mediated correction of matrix metalloproteinase expression promotes re-epithelialization of diabetic wounds

Chronic wounds are a common and costly complication of diabetes, where multifactorial defects contribute to dysregulated skin repair, inflammation, tissue damage, and infection. We previously showed that aspects of the diabetic foot ulcer microbiota were correlated with poor healing outcomes, but ma...

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Published inbioRxiv : the preprint server for biology
Main Authors White, Ellen K, Uberoi, Aayushi, Pan, Jamie Ting-Chun, Ort, Jordan T, Campbell, Amy E, Murga-Garrido, Sofia M, Harris, Jordan C, Bhanap, Preeti, Wei, Monica, Robles, Nelida Y, Gardner, Sue E, Grice, Elizabeth A
Format Journal Article
LanguageEnglish
Published United States 30.06.2023
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Summary:Chronic wounds are a common and costly complication of diabetes, where multifactorial defects contribute to dysregulated skin repair, inflammation, tissue damage, and infection. We previously showed that aspects of the diabetic foot ulcer microbiota were correlated with poor healing outcomes, but many microbial species recovered remain uninvestigated with respect to wound healing. Here we focused on , a Gram-negative bacterium that is frequently recovered from chronic wounds but rarely causes infection. Treatment of diabetic wounds with accelerated healing during early stages. We investigated the underlying mechanisms and found that treatment promotes re-epithelialization of diabetic keratinocytes, a process which is necessary for healing but deficient in chronic wounds. Overexpression of matrix metalloproteinases in diabetes contributes to failed epithelialization, and we found that treatment balances this overexpression to allow proper healing. This work uncovers a mechanism of bacterial-driven wound repair and provides a foundation for the development of microbiota-based wound interventions.