# Impact of hyperglycemia on the pathogenesis of chronic bacterial lung infection

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $223,417

## Abstract

Abstract
Muco-obstructive airway diseases (MADs) are chronic, life-threatening conditions that cause more than 3 million
annual deaths worldwide. MADs are characterized by excess mucus accumulation in the airways, inflammation,
chronic infection, and progressive respiratory failure. Pseudomonas aeruginosa (Pa) is the primary bacterial
pathogen associated with MADs infections. Pa colonization leads to declining lung function, reduced quality of
life, and decreased life expectancy in people with MADs. Diabetes is a frequent comorbidity affecting 18-50% of
individuals with underlying MADs. Diabetes is associated with worse MADs clinical outcomes and increased
susceptibility to severe pulmonary infections. In addition, diabetes is associated with increased antibiotic
treatment failure in individuals with MADs. Utilizing novel in vitro and in vivo model systems, we have observed
increased virulence potential and higher tolerance to antibiotic treatments in Pa under diabetic MADs-like
conditions. These observations raise several questions such as how the diabetic microenvironment in MADs
induces Pa virulence and how it leads to higher rates of antibiotic tolerance. We hypothesize that diabetic
hyperglycemia in the lung microenvironment enhances bacterial fitness and potentiates bacterial
virulence. We further hypothesize that hyperglycemia alters bacterial metabolism towards increased
tolerance to antibiotic therapies. We will address these questions in both in vitro systems that reflect the MADs
and diabetes lung environment and in a diabetic murine chronic infection model of MADs. This proposal will
address key research areas including the influence of diabetes comorbidities in Pa virulence and antibiotic
treatment failure in MADs.

## Key facts

- **NIH application ID:** 10849775
- **Project number:** 5R21AI174088-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Lance R. Thurlow
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $223,417
- **Award type:** 5
- **Project period:** 2023-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10849775

## Citation

> US National Institutes of Health, RePORTER application 10849775, Impact of hyperglycemia on the pathogenesis of chronic bacterial lung infection (5R21AI174088-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10849775. Licensed CC0.

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