Gold nanoclusters exert antibacterial effects against gram-negative bacteria by targeting thiol-redox homeostasis

Low-molecular-weight thiols play a central role in preventing oxidative damage caused by reactive oxygen species to maintain a reductive intracellular environment in bacteria. Therefore, targeting thiol-redox homeostasis is considered a promising antimicrobial strategy. Here, we synthesize histidine-stabilized gold nanoclusters (Au NCs), in which the histidine ligand has a weak affinity for gold, thus constructing an effective thiol scavenger by employing metal-thiol depletion chemicals. Au NCs exert excellent antimicrobial effects by consuming thiols and simultaneously causing the accumulation of reactive oxygen species in bacteria, resulting in severe oxidative stress. In a mouse skin wound model infected with ampicillin-resistant Escherichia coli pHSP70-EGFP, a low dose of Au NCs exerts a strong therapeutic effect on bacterial clearance and wound healing, indicating the effectiveness of this antimicrobial strategy for clinical application.