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.