Mercaptopyrimidine-Conjugated Gold Nanoclusters as Nanoantibiotics for Combating Multidrug-Resistant Superbugs

Widespread bacterial resistance induced by the abuse of antibiotics eagerly needs the exploitation of novel antimicrobial agents and strategies. Gold nanoclusters (Au NCs) have recently emerged as an innovative nanomedicine, but study on their antibacterial properties especially toward multidrug resistant (MDR) bacteria is scarce. Herein, we demonstrate that a novel class of Au NCs, mercaptopyrimidine conjugated Au NCs, can act as potent nanoantibiotics targeting these intractable superbugs in vitro and in vivo, without induction of bacterial antibiotic resistance and noticeable cytotoxicity to mammalian cells. The Au NCs kill these superbugs through a combined mechanism including cell membrane destruction, DNA damage, and reactive oxygen species (ROS) generation, and exhibit excellent treatment effects in both macrophages and animal infection models induced by methicillin-resistant Staphylococcus aureus as representative. Moreover, the induction of intracellular ROS production in bacterial cells mainly attributed to the Au NCs’ intrinsic oxidase- and peroxidase-like catalytic activities has been demonstrated for the first time.