Diabetes Potentiates the Emergence and Expansion of Antibiotic Resistance

Antibiotic resistance is a serious threat to the effective treatment of bacterial infections. People with diabetes frequently develop severe skin and soft tissue infections, predominantly caused by Staphylococcus aureus. Diabetic skin and soft tissue infections are also complicated by increasing rates of antimicrobial resistance. We sought to determine the mechanisms driving the evolution of antibiotic resistance in diabetic skin and soft tissue infections. Herein, we determine that antibiotic resistance rapidly evolves within the diabetic murine model of skin and soft tissue infections. The rapid evolution of resistance is associated with immunosuppression and hyperglycemia. Bacterial TCA cycle activity is important for the emergence of resistance, however it is dispensable for the subsequent propagation of resistant mutants during infection. Importantly, controlling the blood sugar of diabetic mice resulted in significantly decreased incidence of resistant S. aureus.