Accelerated spread of antibiotic resistance genes (ARGs) induced by non-antibiotic conditions: Roles and mechanisms

The global spread of antibiotic resistance genes (ARGs) has wreaked havoc with the treatment efficiency of antibiotics and, ultimately, anti-microbial chemotherapy, and has been conventionally attributed to the abuse and misuse of antibiotics. However, the ancient ARGs have alterative functions in bacterial physiology and thus they could be co-regulated by non-antibiotic conditions. Recent research has demonstrated that many non -antibiotic chemicals such as microplastics, metallic nanoparticles and non-antibiotic drugs, as well as some non-antibiotic conditions, can accelerate the dissemination of ARGs. These results suggested that the role of antibiotics might have been previously overestimated whereas the effects of non-antibiotic conditions were possibly ignored. Thus, in an attempt to fully understand the fate and behavior of ARGs in the eco-system, it is urgent to critically highlight the role and mechanisms of non-antibiotic chemicals and related environmental factors in the spread of ARGs. To this end, this timely review assessed the evolution of ARGs, especially its function alteration, summarized the non-antibiotic chemicals promoting the spread of ARGs, evaluated the non -antibiotic conditions related to ARG dissemination and analyzed the molecular mechanisms related to spread of ARGs induced by the non-antibiotic factors. Finally, this review then provided several critical perspectives for future research.

抗生素抗性基因（ARGs）在全球的传播严重破坏了抗生素以及最终抗菌化学疗法的治疗效果，并且通常被归因于抗生素的滥用和误用。然而，古老的ARGs在细菌生理学中具有替代功能，因此它们可能受到非抗生素条件的共同调控。近期研究表明，许多非抗生素化学物质，如微塑料、金属纳米颗粒和非抗生素药物，以及一些非抗生素条件，都能加速ARGs的传播。这些结果表明，抗生素的作用可能之前被高估了，而非抗生素条件的影响可能被忽视了。因此，为了全面了解ARGs在生态系统中的命运和行为，迫切需要批判性地强调非抗生素化学物质和相关环境因素在ARGs传播中的作用和机制。为此，这篇及时的综述评估了ARGs的演变，特别是其功能改变，总结了促进ARGs传播的非抗生素化学物质，评估了与ARGs传播相关的非抗生素条件，并分析了由非抗生素因素诱导的ARGs传播的分子机制。最后，本综述为未来研究提供了几个关键的视角。