Neutralizing Staphylococcus aureus Virulence with AZD6389, a Three mAb Combination, Accelerates Closure of a Diabetic Polymicrobial Wound
Christine Tkaczyk, Omari Jones-Nelson, Yue Shi, David E. Tabor, Lily Cheng, Tianhui Zhang, Bret R. Sellman
Abstract
Diabetic foot ulcers (DFU) represent a major complication of diabetes and are associated with poor quality of life and increased morbidity and mortality despite standard of care. They have a complex pathogenesis starting with superficial skin lesions, which often progress to deeper tissue structures up to the bone and ultimately require limb amputation. The skin microbiome of diabetic patients has emerged as having an impact on DFU occurrence and chronicity. DFU are mostly polymicrobial, and the Gram-positive bacterium Staphylococcus aureus detected in more than 95% of cases. S. aureus possess a collection of virulence factors which participate in disease progression and may facilitate growth of other pathogens. Here we show in a diabetic mouse wound model that targeting some specific S. aureus virulence factors with a multimechanistic antibody combination accelerated wound closure and promoted full skin re-epithelization. This work opens promising new avenues for the treatment of DFU.