New insights into chronic diabetic wound infections

SUMMARY

Chronic wound infections are a common comorbidity of diabetes mellitus and can progress to amputation if untreated, yet effective strategies to manage these infections are limited. Commensals such as Enterococcus faecium and Staphylococcus epidermidis can transition into opportunistic pathogens when host defences are compromised, underscoring the complexity of chronic wound microbiology. E. faecium, particularly vancomycin-resistant strains, is an understudied, clinically important cause of chronic diabetic wound infections. Using a low-dose streptozocin-induced diabetic mouse model, the authors of this work characterised E. faecium wound infection dynamics and identified differences in colonisation and clearance compared to non-diabetic animals. At 8 h post-infection (hpi), control mice exhibited higher E. faecium wound colony-forming units (CFUs) than diabetic mice but cleared the infection more efficiently, resulting in similar CFU by 24 hpi. By contrast, diabetic mice showed impaired clearance, with elevated CFU persisting through 72 hpi. In mixed species infection with S. epidermidis, S. epidermidis CFU increased at 72 hpi, while E. faecium CFU remained comparable to single species infection. Despite strong initial cytokine and neutrophil responses, E. faecium persisted in all wounds. Sustained neutrophil recruitment at 72 hpi occurred only in diabetic mice, whereas macrophage accumulation increased from 24 to 72 hpi in all wounds, including sterile controls. Histological analysis showed epithelial hyperthickening in both groups, indicating that diabetes and E. faecium each contribute to impaired wound healing. This study establishes a diabetic mouse model of E. faecium wound infection and suggests that E. faecium modulates innate immune responses to persist in the wound bed.

Full article: https://doi.org/10.1128/iai.00652-25

WHY IS THIS IMPORTANT?

Diabetic foot ulcers are difficult-to-heal wounds that affect millions of people worldwide and are a major cause of hospitalisation and limb amputation. This study focused on Enterococcus faecium, a bacterium that is becoming increasingly resistant to antibiotics but is still poorly understood in chronic wound infections. Using diabetic mice, researchers discovered that the bacteria could remain in wounds for several days because diabetic animals had trouble clearing the infection. The bacteria also appeared to change immune responses in the wound, allowing inflammation to continue without successfully removing the infection. In mixed infections, E. faecium also supported the growth of other bacteria commonly found on the skin. These findings are important because they show how diabetes and antibiotic-resistant bacteria can work together to delay healing. The study may guide future treatments aimed at improving immune function and controlling chronic wound infections in diabetic patients.

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