Tuning Ligands Ratio Allows for Controlling Gold Nanocluster Conformation And Activating A Nonantimicrobial Thiol Fragrance for Effective Treatment of MRSA-induced Keratitis.

Bacterial keratitis is a serious ocular disease that affects millions of people worldwide each year, among which ∼25% are caused by Staphylococcus aureus. With the spread of bacterial resistance, refractory keratitis caused by methicillin-resistant Staphylococcus aureus (MRSA) affects ∼120-190 thousand people annually and has become a significant cause of infectious blindness. Atomically precise gold nanoclusters (GNCs) have recently emerged as promising antibacterial agents, although how GNC structure and capping ligands control its antibacterial properties remain largely unexplored. In this study, by adjusting the ratio of a "bulky" thiol fragrance to a linear zwitterionic ligand, the GNC conformation is transformed from Au 25 (SR) 18 to Au 23 (SR) 16 species, simultaneously converting both inactive thiol ligands into potent antibacterial nanomaterials. Surprisingly, mixed-ligand capped Au 23 (SR) 16 GNCs exhibit superior antibacterial potency compared to their mono-ligand counterparts. The optimal GNC is highly potent against MRSA, showing >1024-fold lower minimum inhibitory concentration than the corresponding free ligands. Moreover, it displays excellent potency in treating MRSA-induced keratitis in mice with greatly accelerated corneal recovery (by ∼9-fold). Thus, this study establishes a feasible method to synthesize antibacterial GNCs by adjusting the ligand ratio to control GNC conformation and active non-antibacterial ligands, thereby greatly increasing the repertoires for combating multidrug-resistant bacterial infections. This article is protected by copyright. All rights reserved.