Wednesday, January 15, 2025
1/15/2025
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.
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