Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, China.
J Hazard Mater. 2024 Oct 5;478:135436. doi: 10.1016/j.jhazmat.2024.135436. Epub 2024 Aug 5.
Plasmid-mediated conjugative transfer has emerged as a major driver accounting for the dissemination of antibiotic resistance genes (ARGs). In addition to the use of antimicrobial agents, there is growing evidence that non-antibiotic factors also play an important role. Pesticides are widely used to protect crops against vectors of diseases, and are indispensable agents in agricultural production, whereas the impact of pesticide pollution on the transmission of antimicrobial resistance remains poorly understood. Here we reveal that the pesticides at environmentally relevant concentrations, especially cyromazine (Cyr) and kresoxim-methyl (Kre), greatly facilitate the conjugative transfer of antibiotic-resistance plasmids carrying clinically important ARGs. Mechanistic studies indicate that Cyr and Kre treatments trigger reactive oxygen species (ROS) production and SOS response, increase membrane permeability, upregulate bacterial proton motive force (PMF) and promote ATP supply. Further non-targeted metabolomics and biochemical analysis demonstrate that the addition of Cyr and Kre accelerates tricarboxylic acid (TCA) cycle and electron transport chain (ETC), thereby activating bacterial energy metabolism. In the constructed soil model, we prove that two pesticides contribute to the dissemination of resistance plasmids in the soil microbiota. 16S rRNA sequencing analyses indicate that pesticides alter transconjugant microbial communities, and enable more opportunistic pathogens, such as Pseudomonas and Enterobacter, to acquire the multidrug resistance plasmids. Collectively, our work indicates the potential risk in accelerating the spread of antimicrobial resistance owing to pesticide pollution, highlighting the importance of continuous surveillance of pesticide residues in complex environmental settings.
质粒介导的接合转移已成为导致抗生素耐药基因（ARGs）传播的主要驱动力。除了使用抗菌剂外，越来越多的证据表明，非抗生素因素也起着重要作用。杀虫剂被广泛用于保护作物免受疾病载体的侵害，是农业生产中不可或缺的药剂，而农药污染对抗生素耐药性传播的影响仍知之甚少。在这里，我们揭示了环境相关浓度的农药，特别是环丙氨嗪（Cyr）和克菌壮（Kre），极大地促进了携带临床重要 ARGs 的抗生素抗性质粒的接合转移。机制研究表明，Cyr 和 Kre 处理会引发活性氧（ROS）的产生和 SOS 反应，增加细胞膜通透性，上调细菌质子动力（PMF）并促进 ATP 供应。进一步的非靶向代谢组学和生化分析表明，Cyr 和 Kre 的添加加速了三羧酸（TCA）循环和电子传递链（ETC），从而激活了细菌的能量代谢。在构建的土壤模型中，我们证明了这两种农药有助于在土壤微生物群中传播耐药质粒。16S rRNA 测序分析表明，农药改变了转座子微生物群落，使更多的机会性病原体，如假单胞菌和肠杆菌，能够获得多药耐药质粒。总的来说，我们的工作表明，由于农药污染加速了抗生素耐药性的传播，存在潜在的风险，这凸显了在复杂环境中持续监测农药残留的重要性。
