Chiral Pesticides Selectively Influence the Dissemination of Antibiotic Resistance Genes: An Overlooked Environmental Risk

The global spread of antibiotic resistance genes (ARGs) poses a critical threat to public health and environmental safety. Among environmental factors, the widespread use of chiral pesticides has raised ecological concerns, yet their enantioselective impacts on ARG propagation remain largely unexplored. Here, we investigate how chiral pesticides influence microbial ARG dissemination at the enantiomeric level. Using flurtamone as a model, we successfully separated and quantitatively analyzed its enantiomers (<i>R</i>-flurtamone and <i>S</i>-flurtamone) and evaluated their effects at environmentally relevant concentrations (0-80 μg/L). Remarkably, <i>R</i>-flurtamone significantly enhanced the horizontal transfer of ARGs, surpassing the effects of <i>Rac</i>-flurtamone, whereas <i>S</i>-flurtamone exerted a negligible influence. Mechanistic insights revealed that <i>R</i>-flurtamone is more easily recognized by bacterial cells and induces more cellular stress responses. Additionally, <i>R</i>-flurtamone induced an increase in cell membrane permeability, excessive reactive oxygen species (ROS) production, SOS responses, and boosted ATP levels, further accelerating ARG propagation. By integrating experimental findings with molecular simulations, we elucidated the enantioselective mechanisms underpinning ARG transfer. This study highlights the overlooked risks associated with racemic chiral pesticides at the enantiomeric level and provides a foundation for mitigating ARG dissemination in agricultural and environmental systems.