How Chiral Herbicide Napropamide Modulates Plant Antibiotic Resistance Gene Dissemination: Enantioselective Interference with Nutrient–Metabolite–Cell Wall Networks

Antibiotic resistance genes (ARGs), as emerging contaminants, pose a serious threat to food security and global public health. However, the impact and mechanisms of widely applied herbicides in agriculture, particularly their chiral configurations, on the transfer of ARGs to plants remain unclear. Results revealed that the herbicide napropamide (NAP) <i>R</i>-enantiomer, possessing stronger herbicidal activity against target weeds, reduced ARG accumulation in the nontarget plant <i>Arabidopsis</i> shoots and roots by 54.2 and 36.5%, respectively, compared to the <i>S</i>-enantiomer. In-depth analysis demonstrated this selective regulation linked closely to enantiomer-specific disruptions in plant physiology. <i>R</i>-NAP caused only mild growth inhibition, maintained relatively stable nutrient homeostasis, promoted accumulation of defensive secondary metabolites including nitrogen-containing compounds, flavonoids, and phenolic compounds, and preserved intact cell wall structure. In contrast, <i>S</i>-NAP triggered severe growth suppression, oxidative stress, significant nutrient imbalance, 3-4 fold changes in defense metabolites, and reducing pectin and hemicellulose by 23-32%. Correlation analysis and structural equation modeling quantified that shoot ARG accumulation was primarily governed by nutrient elements and cell wall parameters. Root ARG accumulation was coregulated by the direct action of NAP combined with synergistic effects involving nutrients, secondary metabolites, and cell wall integrity. This work provides a comprehensive theoretical basis for the rational application of herbicides and mitigation of ARG contamination in plants.