Diabetes isn’t just a chronic illness—it’s a breeding ground for superbugs. New research exposes how high blood sugar levels drive antibiotic resistance, making common infections harder to treat and more dangerous than ever.
Study: Diabetes potentiates the emergence and expansion of antibiotic resistance. Image Credit: Shutterstock AI Generator / Shutterstock.com
Diabetes mellitus (DM) affects about 530 million people globally, with current estimates projecting that DM cases will reach 1.3 billion by 2050. Individuals with DM are at an increased risk of skin and soft tissue infections (SSTIs) that are difficult to treat, even with antibiotics.
A recent study published in the journal Science Advances explores the role of DM in the emergence of antimicrobial resistance (AMR) based on the use of antibiotic therapy in Staphylococcus aureus (S. aureus)-associated SSTIs.
What causes SSTIs?
Glucose is the preferred carbon source for several bacterial pathogens. As a result, high concentrations of glucose within the blood can facilitate bacterial growth and virulence, thereby increasing the risk of SSTIs. These infections often worsen rapidly and, as a result, may require amputation of the affected region.
S. aureus, the most common pathogen involved in diabetic SSTIs, preferentially feeds on glucose. In diabetic SSTIs, S. aureus becomes hypervirulent, which, in combination with the immunosuppressive environment and lack of vascularization in diabetic patients, leads to more frequent and severe infections in this patient population.
As a result, people with diabetes are more frequently prescribed antibiotics in an effort to control these infections. In fact, recent studies have identified a 60% increase in antibiotic prescriptions for lower respiratory infections in patients with diabetes.
Previous studies have reported that AMR is more likely to emerge from infections in immunocompromised individuals. AMR is a serious public health concern that was directly responsible for over four million deaths in 2019, with researchers projecting that AMR will cause 10 million deaths by 2050.
About the study
The current study was inspired by the complex interplay between widespread antibiotic usage among diabetic patients and its potential role in propagating AMR. Researchers induced DM in healthy mice and subsequently infected them with a methicillin-resistant S. aureus (MRSA) strain.
Thereafter, mice were treated with systemic rifampicin for four days. Rifampicin is an antibiotic whose resistance develops rapidly by mutations in the rpoB gene. MRSA lesions were assessed for bacterial load throughout the study period.
Study findings
Emergence of resistance
After treatment was completed, rifampicin-resistant (Rif-R) bacteria in the lesions were significantly more abundant in diabetic mice than in non-diabetic animals. Rif-R mutants, 105 colony-forming units (CFUs), emerged from SSTIs in diabetic mice; however, none were recovered from healthy mice.
Rif-R strains exhibited greater tolerance for rifampicin, as demonstrated by the 32,000-fold increase in the minimum inhibitory concentration (MIC) compared to the parental strain. Thus, antibiotic-resistant strains of S. aureus rapidly emerge and expand in diabetic mice but not in non-diabetic mice.
Diabetic environment promotes expansion of Rif-R
Once antibiotic-resistant S. aureus emerged, it rapidly became the dominant or the sole infecting strain in diabetic mice within five days. The diabetic environment promotes the rapid expansion of antibiotic-resistant strains under antibiotic pressure to dominate antibiotic-sensitive strains. Without antibiotic treatment, diabetic and non-diabetic animals yielded similar frequencies of Rif-R strains.
Immunosuppression vs. hyperglycemia
Rifampicin resistance was caused by increased mutation frequency in the rpoB gene. However, DM does not accelerate the frequency of mutations. Rather, the abundant glucose supply supports the growing bacterial population, thereby rapidly increasing the number of replicating cells.
These findings demonstrate that a significantly greater number of potential mutations can be selected under antibiotic pressure in diabetic mice, thus increasing antibiotic resistance. Hyperglycemia is primarily responsible for the expansion of antibiotic-resistant bacterial mutants; however, diabetes-associated immune cell dysfunction also contributes to the emergence of resistance.
Increased VISA growth in diabetic infection
Vancomycin is frequently used to treat MRSA-associated bacteremia. Infection with vancomycin intermediate-resistance S. aureus (VISA) strains are three-fold more common in diabetic patients.
VISA strains are mutants of vancomycin-sensitive S. aureus (VSSA) that are associated with intermediate resistance to vancomycin and, as a result, are less virulent than VSSA. When inoculated into healthy mice, VISA was associated with low reproductive fitness; however, VISA infection in diabetic mice produced larger lesions than those due to the wild-type non-VISA strains in healthy mice.
The administration of insulin to diabetic mice, which partially regulates their blood sugar levels, led to a significant decline in the incidence of antibiotic-resistant S. aureus.
Conclusions
The study findings provide important insights into the role of the diabetic infection microenvironment in the rapid expansion of antibiotic-resistant S. aureus. DM can significantly impact the emergence of S. aureus antibiotic resistance in the future, thus emphasizing the crucial need for antimicrobial compounds to effectively control infections in diabetes patients.
Journal reference:
- Shook, J. C., Genito, C. J., Darwitz, B. P., et al. (2025). Diabetes potentiates the emergence and expansion of antibiotic resistance. Science Advances. doi:10.1126/sciadv.ads1591.