Unveiling the\nAntibacterial Mechanism of Gold Nanoparticles\nby Analyzing Bacterial Metabolism at the Molecular Level

The threat of drug-resistant bacteria is challenging,\nand it is\nurgent to explore new antibiotics. Gold nanoparticles (AuNPs) are\nknown to be a group of promising antibacterial agents for replacing\nconventional antibiotics. Nevertheless, their antibacterial mechanism\nremains to be elucidated. Herein, we directly observed the interaction\nbetween antibacterial AuNPs and bacteria at the molecular level using\nneutral desorption extractive electrospray ionization mass spectrometry\n(ND-EESI-MS). We monitored and analyzed the dynamic changes of bacterial\nmetabolites in real time after AuNP treatment. Ten substances representing\n3 major metabolic pathways, including protein and nucleic acid synthesis,\nenergy metabolism, and quorum sensing, were identified, indicating\nthat AuNPs may exert antibacterial effects through multiple mechanisms\ninfluencing bacterial metabolism and communication. This study deepens\nthe understanding of the antibacterial mechanism of AuNPs and is insightful\nfor designing and screening new antibacterial agents.