Chirality-influenced antibacterial behavior of gold nanoclusters

Abstract

Chirality exists widely in living systems and plays a crucial role in pharmaceutical production and theranostics. Gold nanoclusters (AuNCs) have recently been developed as potential antibacterial therapeutics, but the influence of chirality on their antibacterial behavior is unexplored. Here we prepare ultrasmall L-, D-, and DL-histidine templated AuNCs (denoted as L-AuHis, D-AuHis, and DL-AuHis, respectively) using a simple method. The three AuNCs possess the same physicochemical properties and maintain the chirality consistent with histidine. Antibacterial assay results using Staphylococcus aureus as a representative demonstrate the chirality-influenced antibacterial behavior of these AuNCs. An in-depth investigation revealed that the antibacterial activity of these chiral AuNCs was mainly attributed to cell structure damage and thiol-redox homeostasis imbalance. D-AuHis exhibit more potent antibacterial activity compared to their enantiomers. This difference in antibacterial behavior is mainly since the L-AuHis and DL-AuHis can react with bacterial cell wall components, such as lipoteichoic acid, to form large-sized nanoparticles, thereby weakening the antibacterial activity compared with the D-AuHis. The antibacterial effect of AuHis was further validated in a bacterial-infected wound model. Our findings provide a deeper insight into the establishment of unique chiral inorganic antibacterial constructions and hint at the potentiality of dextrorotatory AuNCs having strengthened antibiotic activity.