Inhibition of quorum sensing serves as an effective strategy to mitigate the risks of human bacterial pathogens in soil.

The coexistence of antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and virulence factor genes (VFGs) in human bacterial pathogens (HBPs) increases their risks to ecological security and human health and no effective strategy is available. Herein, we demonstrated two typical quorum sensing (QS) interfering agents, 4-nitropyridine-N-oxide (4-NPO, a QS inhibitor) and Acylase Ⅰ (a quorum quenching (QQ) enzyme), effectively decreased the abundance of HBPs by 48.30% and 72.54%, respectively, which was accompanied by the reduction of VFGs, ARGs, and MGEs. The decrease in QS signals mediated by QS interfering agents disturbed bacterial communication and inhibited biofilm formation. More importantly, QS interfering agents reduced the intra-species and inter-species conjugation frequencies among bacteria, considerably inhibiting the dissemination of ARGs and VFGs via horizontal gene transfer. Furthermore, the QS interfering agents did not significantly affect the metabolic function of other nonpathogenic microorganisms in the soil. Collectively, our study provides an effective and eco-friendly strategy to mitigate the risks of HBPs in soil.