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

Ellen K. White; Aayushi Uberoi; Jamie Ting-Chun Pan; Jordan T. Ort; Amy E. Campbell; Sofia M. Murga-Garrido; Jordan C. Harris; Preeti Bhanap; Monica Wei; Nelida Y. Robles; Sue E. Gardner; Elizabeth A. Grice

doi:10.1101/2023.06.30.547263

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

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

Ellen K. White, Aayushi Uberoi, Jamie Ting-Chun Pan, Jordan T. Ort, Amy E. Campbell, Sofia M. Murga-Garrido, Jordan C. Harris, Preeti Bhanap, Monica Wei, Nelida Y. Robles, …

bioRxiv

Cold Spring Harbor Laboratory

06/30/2023

DOI: 10.1101/2023.06.30.547263

PMCID: PMC10327199

PMID: 37425836

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https://doi.org/10.1101/2023.06.30.547263View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

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 Alcaligenes faecalis , a Gram-negative bacterium that is frequently recovered from chronic wounds but rarely causes infection. Treatment of diabetic wounds with A. faecalis accelerated healing during early stages. We investigated the underlying mechanisms and found that A. faecalis 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 A. faecalis 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.

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Title: Subtitle: Wound microbiota-mediated correction of matrix metalloproteinase expression promotes re-epithelialization of diabetic wounds
Creators: Ellen K. White - University of Pennsylvania
Aayushi Uberoi - University of Pennsylvania
Jamie Ting-Chun Pan - University of Pennsylvania
Jordan T. Ort - University of Pennsylvania
Amy E. Campbell - University of Pennsylvania
Sofia M. Murga-Garrido - University of Pennsylvania
Jordan C. Harris - University of Pennsylvania
Preeti Bhanap - University of Pennsylvania
Monica Wei - University of Pennsylvania
Nelida Y. Robles - University of Pennsylvania
Sue E. Gardner - University of Iowa
Elizabeth A. Grice - University of Pennsylvania
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2023.06.30.547263
PMID: 37425836
PMCID: PMC10327199
Publisher: Cold Spring Harbor Laboratory
Language: English
Date posted: 06/30/2023
Academic Unit: Nursing
Record Identifier: 9984442222602771

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