A multifunctional antibacterial nanozyme for eradicating multidrug-resistant bacteria and promoting wound repair

Abstract The escalating global threat of multidrug-resistant (MDR) bacterial infections necessitates the development of alternative therapeutic strategies beyond traditional antibiotics. In this study, we synthesized gold-copper alloy (AuCu3) nanozymes to address this challenge and investigated their catalytic efficiency, mechanisms, and interactions with the host immune system. We employed in vitro assays against carbapenem-resistant Klebsiella pneumoniae (CRKP), murine infection models, and clinical cases of otitis externa to evaluate therapeutic efficacy. Furthermore, single-cell RNA sequencing was utilized to elucidate the underlying immunomodulatory pathways. Our results demonstrate that AuCu3 nanozymes exhibit potent peroxidase-like activity, catalyzing the conversion of hydrogen peroxide (H2O2) into cytotoxic hydroxyl radicals. This reaction achieves broad-spectrum, irreversible bacterial elimination within three hours through synergistic membrane disruption and DNA degradation. In both animal models and clinical applications, the AuCu3/H2O2 system effectively eradicated MDR infections and accelerated tissue repair without inducing systemic toxicity. Mechanistically, transcriptomic analysis revealed that AuCu3 triggers immunometabolic reprogramming in monocytes, shifting their metabolism from glycolysis to oxidative phosphorylation. This metabolic transition enhances innate immune recruitment, while concurrent activation of copper homeostatic pathways ensures cellular equilibrium. Consequently, AuCu3 represents a promising dual-action therapeutic platform that combines direct antimicrobial activity with host-directed immune modulation to combat intractable infections and promote wound healing.