Repurposing sulfamethoxazole via gold nanocluster modification for antibacterial and anti-biofilm activity against
Yiwen Xue1, Yujing Wang2, Congcong You2
1Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Objectives:
The global spread of antimicrobial resistance represents a severe threat to public health, with infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) emerging as a major clinical challenge. The clinical utility of traditional antimicrobial agents, such as sulfamethoxazole (SMZ), has become increasingly restricted by the emergence of bacterial resistance. Recent advances in nanomedicine have opened opportunities for 'old drugs, new uses' strategies to improve the antibacterial performance of existing agents.
Methods:
We synthesized SMZ-modified gold nanoclusters (SMZ_Au NCs) via a green one-pot method and evaluated their antibacterial and anti-biofilm activities, underlying mechanisms, biocompatibility, and in vivo therapeutic efficacy against clinical MDR-GNB isolates using multiple in vitro assays and murine infection models.
Results:
SMZ_Au NCs exhibited enhanced antibacterial activity with substantially reduced minimum inhibitory concentrations compared with SMZ alone, inhibited biofilm formation, and partially disrupted established biofilms. Mechanistic investigations suggested that the antibacterial effects were primarily associated with membrane perturbation and disruption of bacterial homeostasis, accompanied by moderate increases in intracellular reactive oxygen species. Initial in vitro biocompatibility assessments demonstrated that SMZ_Au NCs were well tolerated up to 32 µg/mL, and in vivo studies showed no acute toxicity at antibacterial-relevant doses. Moreover, SMZ_Au NCs demonstrated therapeutic efficacy in murine infection models, supporting their in vivo antibacterial potential at a proof-of-concept level.
Conclusions:
Nanocluster-based modification may provide a feasible approach to enhance sulphonamide antibacterial performance and support further investigation of SMZ_Au NCs against MDR-GNB infections.
