Diabetes boosts antibiotic resistance in mice

Colorized scanning electron micrograph of methicillin-resistant Staphylococcus aureus (MRSA) bacteria. NIAID

People with diabetes tend to get more infections than those without. This is in part because people with diabetes have too much sugar, or glucose, in their blood, which promotes bacterial growth. Diabetes also suppresses the immune system, which makes it hard to fight infections. These factors can raise the risk of developing bacterial infections of the skin and soft tissues, including tendons and ligaments. Severe infections may require amputation of toes, feet, or other extremities.

Diabetic skin and tissue infections are often treated with antibiotics, but drug-resistant bacteria are a growing concern. Staphylococcus aureus, or staph, is the most common cause of such infections in people with diabetes. But the underlying links between diabetes, bacterial infection, and antibiotic resistance have been unclear.

A research team led by Drs. Brian Conlon and Lance Thurlow of the University of North Carolina set out to learn more. The scientists began by giving diabetic and non-diabetic mice skin infections with S. aureus. The mice then received four daily treatments with the antibiotic rifampicin. S. aureus is prone to develop rapid resistance to this drug. The results appeared in Science Advances on February 12, 2025.

A day after antibiotic treatment had ended, the researchers found that S. aureus levels were significantly higher in diabetic than in non-diabetic mice. This was expected, since diabetes can fuel the growth of bacteria. But the scientists also found that the diabetic mice quickly evolved resistance to the antibiotic over just a four-day period. In contrast, no signs of antibiotic resistance were observed in the non-diabetic mice. Additional studies showed that when drug-resistant strains of S. aureus emerge, their numbers rapidly expand during antibiotic treatment.

The researchers assessed different factors that could lead to this increased drug resistance. They found that faulty immune cells contribute to the emergence of drug resistance in mice with diabetes. However, high glucose levels, or hyperglycemia, has a much larger impact. 

In a final experiment, the scientists assessed the effects of improved glucose control. They gave daily doses of insulin to diabetic mice. These insulin treatments only partially normalized blood glucose levels. Yet they significantly reduced the emergence of drug-resistant bacteria. Taken together, the results suggest that even partial control of blood glucose may help to combat antibiotic resistance.

“Resistance and its spread are not only associated with the prescription of drugs, but also the health status of those that are taking antibiotics,” Conlon says. “Controlling blood glucose then becomes really important. When we gave our mice insulin, we were able to bring their blood sugar back to normal and we didn't get this rapid proliferation of resistant bacteria.”

The findings suggest that improved glucose control could help prevent the emergence of drug-resistant bacteria in people with diabetes.

—by Vicki Contie