This proposal aims to establish proof of concept that i) downregulation of PPAR and impaired adipogenesis are a result of the dissemination of Group A Streptococcus (GAS) bacteria into the adipose niche during Necrotizing Soft Tissue Infections (NSTI), and ii) activation of PPAR by specific ligands might have a positive effect on reversing the impaired adipogenesis. Our studies aim to advance the understanding of the metabolic consequences and pathophysiological mechanisms underlying NSTI in varying genetic contexts for designing novel diagnostic and personalized therapeutic strategies to improve NSTI outcomes. The information gained from the proposed studies will present us with knowledge of hostdirected approaches as feasible adjuncts to antibiotic therapy and substantially transform the therapeutic strategies to promote favorable outcomes of NSTI and create healthy adipose tissue homeostasis.