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The Diabetic Wound Environment Shapes Group B Streptococcal Pathogenesis

Award Number: K99AI180373
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 06/13/2024
PERIOD OF PERFORMANCE END DATE: 01/04/2026

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The Diabetic Wound Environment Shapes Group B Streptococcal Pathogenesis - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$15,908 )
2026	2025	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Allergy and Infectious Diseases Research	000	2	1/21/2026	NON-COMPETING CONTINUATION	-$15,908
														Subtotal = -$15,908

Issue Date FY: 2025 ( Subtotal = $100,000 )
2025	2025	THE REGENTS OF THE UNIV. OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Allergy and Infectious Diseases Research	001	2	5/16/2025	NON-COMPETING CONTINUATION	$100,000
2025	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Allergy and Infectious Diseases Research	000	1	11/14/2024	NEW	$0
														Subtotal = $100,000

Issue Date FY: 2024 ( Subtotal = $100,000 )
2024	2024	THE REGENTS OF THE UNIVERSITY OF COLORADO	13001 E 17TH PL STE F428	AURORA	CO	80045	ADAMS	USA	Allergy and Infectious Diseases Research	000	1	6/13/2024	NEW	$100,000
														Subtotal = $100,000

Grand Total All Awards = $184,092

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The Diabetic Wound Environment Shapes Group B Streptococcal Pathogenesis

Award Number: K99AI180373

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 06/13/2024

PERIOD OF PERFORMANCE END DATE: 01/04/2026

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