# The Diabetic Wound Environment Shapes Group B Streptococcal Pathogenesis

> **NIH NIH K99** · UNIVERSITY OF COLORADO DENVER · 2024 · $100,000

## Abstract

PROJECT SUMMARY
Diabetic wound infections are a major public health burden, with approximately 25% of diabetic individuals
developing a wound in their lifetime, 25% of these wounds not healing and 28% requiring surgical amputation.
The diabetic wound environment is complex, with hyperglycemia driving immune dysfunction and bacterial
pathogenesis leading to poor infection outcomes. One of the most frequently isolated bacterial species from
diabetic wound infections is Group B Streptococcus (GBS). Interestingly, GBS is notoriously absent from non-
diabetic wounds, suggesting that components of the diabetic environment specifically influence GBS success in
this niche. Previously, I have developed two murine models of GBS diabetic wound infection and determined
that GBS promotes hyper-inflammation in vivo. Dual RNA-sequencing of the murine and GBS transcriptome has
identified multiple host and bacterial targets with altered transcription during diabetic infection that have informed
the hypothesis herein. This proposal therefore seeks to elucidate the environmental factors that promote GBS
infection of diabetic wounds. I hypothesize that multiple facets of the diabetic wound environment including
neutrophil function, hyperglycemia and polymicrobial interactions contribute to GBS success. This hypothesis
will be addressed via the following specific aims: Aim 1: Evaluate the consequences of altered neutrophil function
to GBS pathogenesis during diabetic wound infection. Aim 2: Determine how hyperglycemia contributes to GBS
pathogenesis in the diabetic wound. Aim 3: Examine the contribution of Staphylococcus aureus to GBS diabetic
wound persistence during polymicrobial infection. These studies will increase our understanding of how the
diabetic wound differs from the non-diabetic wound environment, and the consequences of that altered
environment on pathogen success.

## Key facts

- **NIH application ID:** 10984829
- **Project number:** 1K99AI180373-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Rebecca Keogh
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $100,000
- **Award type:** 1
- **Project period:** 2024-06-13 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10984829

## Citation

> US National Institutes of Health, RePORTER application 10984829, The Diabetic Wound Environment Shapes Group B Streptococcal Pathogenesis (1K99AI180373-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10984829. Licensed CC0.

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