Chiral pesticide permethrin promotes the antibiotic resistance genes dissemination by transformation: Different chiral isomers engage in distinct regulatory pathways

The global dissemination of antibiotic resistance genes (ARGs) poses an increasingly urgent threat to both environmental and human health. The extensive use of chiral permethrin (PM), the most popular synthetic type I pyrethroid insecticide worldwide, has led to its increased detection in aquatic environments. However, our understanding of PM's role in spreading ARGs is still limited. Here, we systematically assessed the effects of two chiral isomers of 1R-cis-PM (CPM) and 1R-trans-PM (TPM) on the dissemination of ARGs in the aquatic environments by using a natural transformation (NT) model comprising plasmid pWH1274 and Acinetobacter baylyi ADP1. It was found that reactive oxygen species (ROS) was the main factor facilitating the NT of ARGs mediated by CPM and TPM, although their respective production mechanisms exhibited distinct pathways: CPM generates ROS primarily through the primary electron transport chain (ETC), whereas TPM does so via a secondary ETC. Furthermore, CPM enhanced NT by improving bacterial competent state, while TPM promotes it by enhancing recombination. It was confirmed that both CPM and TPM have the potential to accelerate the spread of ARGs through distinct mechanisms. These findings will help us understand that different chiral isomers may pose risks through distinct mechanisms.