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Diabetes potentiates the emergence and expansion of antibiotic resistance

John C Shook1, Christopher J Genito2, Benjamin P Darwitz1

  • 1Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Science Advances
|February 12, 2025
PubMed

Insights

Diabetes accelerates antibiotic resistance in Staphylococcus aureus skin infections. Hyperglycemia, not immune dysfunction, drives resistance, suggesting blood sugar control can reduce resistant bacteria.

Area of Science:

  • Microbiology
  • Immunology
  • Metabolic Disorders

Background:

  • Diabetes mellitus significantly increases the risk of severe skin and soft tissue infections (SSTIs).
  • These infections are often difficult to treat with antibiotics, raising concerns about antibiotic resistance.
  • Staphylococcus aureus is a common pathogen in SSTIs.

Purpose of the Study:

  • To investigate the impact of diabetes on the emergence of antibiotic resistance in Staphylococcus aureus SSTIs.
  • To determine the roles of hyperglycemia and immune cell dysfunction in driving antibiotic resistance.
  • To assess the potential of glycemic control in mitigating antibiotic resistance.

Main Methods:

  • Comparative analysis of Staphylococcus aureus SSTI development in diabetic and nondiabetic mice.
  • Assessment of antibiotic resistance evolution over the course of infection.
  • Evaluation of the contribution of hyperglycemia and immune cell dysfunction.
  • Testing the effect of insulin treatment on antibiotic resistance incidence.

Main Results:

  • Staphylococcus aureus rapidly evolved antibiotic resistance in diabetic mice, unlike in nondiabetic mice.
  • Hyperglycemia was identified as the primary driver of antibiotic resistance, with immune cell dysfunction playing a minor role.
  • Vancomycin-intermediate resistant isolates showed reduced fitness in nondiabetic mice but not in diabetic mice.
  • Insulin treatment to control blood sugar significantly decreased the incidence of antibiotic-resistant Staphylococcus aureus.

Conclusions:

  • The diabetic infection environment acts as a reservoir for the emergence and proliferation of antibiotic resistance.
  • Hyperglycemia is a critical factor promoting antibiotic resistance in Staphylococcus aureus SSTIs.
  • Controlling blood glucose levels is a potential strategy to reduce the incidence of antibiotic-resistant infections in diabetic individuals.

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