# Diabetes and Antibiotic Treatment Failure

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $684,320

## Abstract

Abstract
Skin and soft tissue infection (SSTI) is a major complication in diabetic patients and Staphylococcus aureus is
the most common causative organism. Antibiotics frequently fail to clear these infections, leading to chronic
infection and progression to more severe infections such osteomyelitis and bacteremia. The reasons for the high
rates of treatment failure in diabetic patients remain unclear.
We employ a murine SSTI model with normal and diabetic mice and methicillin-resistant Staphylococcus aureus
(MRSA). We observe increased antibiotic tolerance and spontaneous antibiotic resistance (mutation) in diabetic
mice infected with MRSA, compared to the infected normal mice. We also observe a 10-fold increase in glucose
concentrations in the diabetic infection environment. We hypothesize that excess glucose in the diabetic infection
environment alters bacterial and host metabolism driving antibiotic tolerance and resistance.
In aim 1 we will examine how excess glucose primes glycolysis in S. aureus, leading to acidification of the
infection microenvironment and increased mutagenesis, resulting in antibiotic tolerance and resistance. In aim 2
we will examine how incapacitation of the immune system in diabetic mice may be inducing reservoirs of
antibiotic tolerant and resistant S. aureus during infection. In aim 3, we will examine the in-host evolution of
antibiotic tolerance, resistance, and fitness during sequential infection of diabetic mice to determine the
progression of mutations that result in highly virulent, antibiotic resistant strains that are likely highly deleterious
to the patient.
Determining how blood glucose levels contribute to the development of antibiotic resistance will be an important
development and will further emphasize the importance of treating and preventing diabetes, particularly as rates
continue to rise annually.

## Key facts

- **NIH application ID:** 10739807
- **Project number:** 5R01AI173004-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Brian Patrick Conlon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $684,320
- **Award type:** 5
- **Project period:** 2022-11-14 → 2027-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10739807

## Citation

> US National Institutes of Health, RePORTER application 10739807, Diabetes and Antibiotic Treatment Failure (5R01AI173004-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10739807. Licensed CC0.

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