# Skin microbial-based mechanisms of accelerated wound healing

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2022 · $34,191

## Abstract

PROJECT SUMMARY
 Improved therapeutic approaches are needed for non-healing wounds, as they present a major
challenge to the healthcare system by increasing treatment costs as well as rates of morbidity and mortality.
The skin microbiome exists at the interface of all cutaneous wounds, but its potential as a novel therapeutic
target remains untapped. Therefore, our long-term goal is to understand host-microbial interactions during
wound healing, so we may leverage these mechanisms to identify wound healing treatments. To initiate this
investigation, our lab previously performed a metagenomic analysis on wound samples from non-infected
diabetic foot ulcers (DFUs) and unearthed a surprisingly prevalent wound inhabitant Alcaligenes faecalis. Very
little is known about this species in the context of wounds, so we sought to investigate the effect of A. faecalis
on wound healing. We observed the surprising finding that treating wounds with A. faecalis accelerates the rate
of wound healing in vivo and activates a pro-epithelialization phenotype in keratinocytes. Thus, the central goal
of this study is to identify the mechanism by which A. faecalis mediates accelerated wound healing. Pro-
inflammatory cytokine signaling is necessary to promote re-epithelialization, and IL-6 in particular has been
shown to induce activation of keratinocytes during healing. Therefore, I tested if A. faecalis induced a cytokine
response in keratinocytes and found robust IL-6 production after treatment with A. faecalis conditioned media.
A primary mechanism by which bacteria can modulate host responses is through production of secreted
molecules. I found that sterile supernatant of A. faecalis, rather than bacterial-cell surface molecules, promotes
keratinocyte migration and IL-6 production. Together, these findings lead to my hypothesis that A. faecalis
produces secreted molecules that improve re-epithelialization by enhancing keratinocyte IL-6 signaling. Aim 1
will determine the host mechanisms of A. faecalis-induced accelerated healing through a combination of
wound healing assays and transcriptional profiling. Aim 2 will identify the microbial genetic determinants of A.
faecalis necessary to produce the pro-healing secreted molecule. I will use comparative genomics approach to
identify genomic loci that segregate with a pro-wound healing phenotype. To complete this aim, I will leverage
our collection of 44 A. faecalis clinical DFU isolates and perform a genomic multiple alignment. I will pair this
genetic screen with a phenotypic screen using wound healing assays to determine which genomic locus
segregates with the pro-healing phenotype.
 In conjunction with these experimental aims, I will also engage in a rigorous training plan at the
University of Pennsylvania under the guidance of the MD/PhD Program and my PhD advisor. This training plan
will foster my development as a future physician scientist through the following goals: strengthen
independence as an investigator, ...

## Key facts

- **NIH application ID:** 10464143
- **Project number:** 1F31AR079852-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Ellen White
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $34,191
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464143

## Citation

> US National Institutes of Health, RePORTER application 10464143, Skin microbial-based mechanisms of accelerated wound healing (1F31AR079852-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10464143. Licensed CC0.

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