# Factors Leading to Enhanced Pseudomonas Aeruginosa Infection in Diabetic Wounds

> **NIH NIH R01** · RUSH UNIVERSITY MEDICAL CENTER · 2020 · $348,750

## Abstract

Foot ulcers are one of the leading causes of hospitalization for people with diabetes in the developed world and a
major morbidity associated with diabetes leading to pain, suffering, and a poor quality of life for patients. 25.8
million patients with diabetes in US alone develop foot ulcers at some point in their lives, costing approximately 25
billion dollars in care annually and accounting for 67% of all lower extremity amputations in the US. Bacterial
infection has been long recognized as a major impediment to wound healing in diabetic ulcers. A shift in the
microbiome toward pathogenic bacteria, such as Pseudomonas aeruginosa occurs in diabetic ulcers and
correlates with a poor healing prognosis. The underlying reasons for the inability of diabetic wounds to fight off
bacterial infection and the reasons for the microbiome shift toward pathogenic bacteria remain poorly understood.
Based on our preliminary data, our central hypothesis is that inadequate neutrophil infiltration early after injury in
diabetic wound-- due to impaired neutrophil chemotactic response through the formylated peptide receptor (FPR)
-- leads to reduced TLR signaling, reduced inflammatory responses, and reduced pathogen-specific AMP
expression, rendering diabetic wound vulnerable to infection with pathogenic bacteria, which further exacerbate
diabetic wound, driving it toward hyper-inflammatory and chronic state. In this proposal, we will: (Aim 1) determine
the molecular mechanisms that underlie the impaired neutrophil response in diabetic wound; (Aim 2) assess the
adverse impact of delayed neutrophil response on signaling through pattern recognition receptors (PRRs); and
(Aim 3) assess the adverse impact of delayed neutrophil response on antimicrobial peptides (AMPs) productions,
particularly the pathogen-specific AMPs that render diabetic wounds vulnerable to colonization and microbiome
shift toward Pseudomonas aeruginosa. We will also evaluate the therapeutic potential of pro-inflammatory
chemokines and Toll-like receptor ligands to restore antimicrobial defenses and stimulate healing by jumpstarting
the neutrophil response in diabetic wounds early after injury.

## Key facts

- **NIH application ID:** 9974298
- **Project number:** 5R01DK107713-05
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** SASHA H SHAFIKHANI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $348,750
- **Award type:** 5
- **Project period:** 2016-09-20 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974298

## Citation

> US National Institutes of Health, RePORTER application 9974298, Factors Leading to Enhanced Pseudomonas Aeruginosa Infection in Diabetic Wounds (5R01DK107713-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9974298. Licensed CC0.

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