Metal-based nanomaterials as antimicrobial agents: A novel driveway to accelerate the aggravation of antibiotic resistance

The consequences of antibiotic tolerance directly affect human health and result in socioeconomic loss. Nanomaterials as antimicrobial agents are considered a promising alternative to antibiotics and have been blended with various medical applications. However, with increasing evidence that metal-based nanomaterials may induce antibiotic tolerance, there is an urgent need to scrutinize how nanomaterial-induced microbial adaption affects the evolution and spread of antibiotic tolerance. Accordingly, within this investigation, we summarized the principal factors influencing the resistance development exposed to metal-based nanomaterials, including physicochemical properties, exposure scenario, as well as bacterial response. Furthermore, the mechanisms of metal-based nanomaterial-induced antibiotic resistance development were comprehensively elucidated from acquired resistance by horizontal transfer of antibiotic resistance genes (ARGs), intrinsic resistance by genetic mutation or upregulated resistance-related gene expression, and adaptive resistance by global evolution. Overall, our review raises concerns about the safety of nanomaterials as antimicrobial agents, which will facilitate assistance in the safe development of antibiotic-free antibacterial strategies.