# Decoding the microbial burden in diabetic foot ulcers

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $511,458

## Abstract

Chronic, non-healing wounds are common and costly complications of diabetes. Microbial colonization and
biofilm formation are hypothesized to impair wound healing and contribute to severe complications such as
osteomyelitis and amputation. Although all chronic wounds are colonized with microbiota, its importance, in the
absence of clinical infection, is currently unknown. In this competitive renewal, we hypothesize that host
response, wound healing, and clinical DFU outcomes are determined by 1) genomic diversification of the
wound pathogen Staphylococcus aureus; 2) commensal interactions with wound pathogens; and 3)
commensal interactions with the host. In the previous cycle, we developed a shotgun metagenomic
sequencing pipeline to analyze the microbiota colonizing neuropathic, non-infected DFU (n=100; the “DFU100”
cohort) in a longitudinal prospective cohort study. We observed that strain-level variation of the wound
pathogen Staphylococcus aureus was associated with DFU outcomes. Therefore, in Aim 1, we will use a
microbial genomic approach and matched clinical isolates from the DFU100 cohort to identify S. aureus
genomic determinants of pathogenesis in DFU and their association with clinical outcomes. We also observed
that species clinically regarded as “bystanders” (e.g. skin commensals, environmental contaminants) influence
the virulence of wound pathogens and tune host tissue repair responses to promote healing in vivo. Aim 2 will
determine if a skin commensal, Corynebacterium striatum, tunes the virulence of S. aureus and improves
wound healing in murine and porcine models of S. aureus wound infection. Aim 3 is based on our observation
that Alcaligenes faecalis wound isolates promote keratinocyte migration, cytokine secretion, and accelerated
wound closure in a murine model of diabetic wound healing. We will establish the mechanism and therapeutic
potential of A. faecalis-mediated host responses that lead to accelerated wound healing. The proposed
research will use cutting-edge, cross-disciplinary approaches to investigate interactions between wound
pathogens, wound “bystanders”, and the host; understanding these mechanisms will lead to improved DFU
outcomes as our long-term objectives are to 1) develop novel microbiota-based interventions to improve
healing that exploit microbial interactions with each other and the host; and 2) identify microbial biomarkers to
classify patients at risk of complication.

## Key facts

- **NIH application ID:** 9989920
- **Project number:** 5R01NR015639-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Elizabeth Anne Grice
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $511,458
- **Award type:** 5
- **Project period:** 2015-05-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989920

## Citation

> US National Institutes of Health, RePORTER application 9989920, Decoding the microbial burden in diabetic foot ulcers (5R01NR015639-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9989920. Licensed CC0.

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