Biofilm-Associated Infections in Diabetes: Microbial Virulence, Oxidative Stress, and Impaired Wound Healing

Diabetes mellitus increases the risk for chronic and recurrent infections, including diabetic foot infections and nonhealing wounds. Biofilms are complex microbial communities encased in extracellular polymeric substances that they manufacture themselves, and that favour infection persistence, antimicrobial tolerance, immunological evasion, and delayed tissue repair. The diabetic wound environment, which favours biofilm formation, is characterised by hyperglycaemia, poor peripheral circulation, neuropathy, immunological dysfunction and protracted inflammation. Important microbial infections include Staphylococcus aureus, Pseudomonas aeruginosa, enterococci and a number of Gram-negative bacilli. Polymicrobial communities are sometimes encountered. Microbial virulence elements comprising adhesins, toxins, quorum-sensing systems, extracellular enzymes and matrix components linked with biofilm formation allow colonisation and tissue injury. Simultaneously, oxidative stress, mitochondrial dysfunction, advanced glycation end-product production and poor antioxidant defences generated by hyperglycaemia impede cellular signalling, angiogenesis, collagen deposition and epithelial regeneration. Microbial biofilms interacting with oxidative stress produce a self-perpetuating inflammatory milieu which hinders normal wound progression. This study discusses the microbiological mechanisms involved in biofilm infections in diabetes, the biochemical pathways linking oxidative stress and impaired wound healing and the clinical consequences in terms of diagnosis and management. It stresses the necessity of appropriate microbiological assessment, glycaemic control, wound debridement, pressure off-loading, vascular assessment and antimicrobial stewardship. Novel treatment techniques with potential benefits include antibiofilm agents, targeted medication delivery, quorum-sensing inhibition, and molecular diagnostics, however these require further clinical confirmation.