Inducing Ferroptosis-like Death in Pseudomonas aeruginosa Combined with Bacteriophage Therapy for Burn Wound Infection Treatment

Conventional antibiotics have limited efficacy against drug-resistant Pseudomonas aeruginosa infections in burn wounds, underscoring the urgent need for alternative therapeutic strategies. Here, we developed a synergistic approach that combines iron ion-induced ferroptosis-like death with bacteriophage therapy, and evaluated its antibacterial efficacy and wound healing capacity. A lytic bacteriophage specific for P. aeruginosa was isolated from hospital sewage and characterized. Mechanistic studies revealed that Fe³⁺ treatment induced bacterial death characterized by reactive oxygen species accumulation, lipid peroxidation, DNA damage, and biofilm inhibition—hallmarks of ferroptosis. To enable local co-delivery, both agents were encapsulated in a sodium alginate hydrogel. This composite system exhibited potent synergistic antibacterial activity in vitro. In a mouse model of infected burn wounds, the combination therapy significantly accelerated wound closure and granulation tissue formation during the early phase, while reducing inflammatory infiltration and abnormal collagen deposition in the late phase. These findings demonstrate that ferroptosis induction and phage therapy act synergistically, and that the alginate hydrogel serves as an effective local delivery platform, offering a promising new strategy for treating drug-resistant burn infections.