Multiplex antibacterial processes and risk in resistant phenotype by high oxidation-state nanoparticles: New killing process and mechanism investigations

Although inorganic silver-based nanoparticles (NPs) have been used to replace antibiotics to treat environmental microorganisms, the silver ion diffusion mechanism takes at least hours to poison the bacteria and cannot destruct the bacteria immediately. In this paper, we developed a concise oxidation process of heterostructured Ag@AuAg hollow NPs in a H₂O₂/PBS solution to generate AgCl nanocrystals and high-oxidation-state (hos) metal species. The hos/AgCl-assembled NPs offered a strong redox reaction to kill bacteria at 1.25 ppm_[Ag] which was lower minimal inhibition concentration value than the utility of Ag ions and Ag NPs. A rapid meet-dip-kill process to disintegrate the bacterial membrane was observed within 60 min. The continuous release of Ag ions from AgCl blocks served as a smart bactericide to sustainably inhibit bacterial growth up to 7 days. The hos/AgCl-based bactericide induced enhanced evolution of a distinctive subpopulation with rigid membrane structure against both Ag ions and Ag-based NPs. This Ag-resistant persister behaved the downregulation of energy consumption and the physical insulation for Ag ions by secreting bio-reductants to convert Ag ions to less toxic Ag NPs. Based on our findings, hos/AgCl-assembled NPs endowed multiple antibacterial effects with no prominent findings of toxicity in the liver and kidneys, which opens a new era to understand the antimicrobial mechanism and resistant risk of Ag-related NPs for future clinical and environmental application.