School of Ecology and Environment, Ningxia University, Yinchuan 750021, PR China; Key Laboratory of Low-carbon Green Agriculture in Northwestern China, Ministry of Agriculture and Rural Affairs; College of Natural Resources and Environment, Northwest A&F University, Yangling, Shaanxi Province 712100, PR China.
Key Laboratory of Low-carbon Green Agriculture in Northwestern China, Ministry of Agriculture and Rural Affairs; College of Natural Resources and Environment, Northwest A&F University, Yangling, Shaanxi Province 712100, PR China.
Water Res. 2024 Jun 15;257:121659. doi: 10.1016/j.watres.2024.121659. Epub 2024 Apr 25.
Various heavy metals are reported to be able to accelerate horizontal transfer of antibiotic resistance genes (ARGs). In real water environmental settings, ubiquitous complexing agents would affect the environmental behaviors of heavy metal ions due to the formation of metal-organic complexes. However, little is known whether the presence of complexing agents would change horizontal gene transfer due to heavy metal exposure. This study aimed to fill this gap by investigating the impacts of a typical complexing agent ethylenediaminetetraacetic acid (EDTA) on the conjugative transfer of plasmid-mediated ARGs induced by a range of heavy metal ions. At the environmentally relevant concentration (0.64 mg L) of metal ions, all the tested metal ions (Mg, Ca, Co, Pb, Ni, Cu, and Fe) promoted conjugative transfer of ARGs, while an inhibitory effect was observed at a relatively higher concentration (3.20 mg L). In contrast, EDTA (0.64 mg L) alleviated the effects of metal ions on ARGs conjugation transfer, evidenced by 11 %-66 % reduction in the conjugate transfer frequency. Molecular docking and dynamics simulations disclosed that this is attributed to the stronger binding of metal ions with the lipids in cell membranes. Under metal-EDTA exposure, gene expressions related to oxidative stress response, cell membrane permeability, intercellular contact, energy driving force, mobilization, and channels of plasmid transfer were suppressed compared with the metal ions exposure. This study offers insights into the alleviation mechanisms of complexing agents on ARGs transfer induced by free metal ions.
各种重金属被报道能够加速抗生素耐药基因（ARGs）的水平转移。在实际的水环境中，由于金属-有机配合物的形成，普遍存在的络合剂会影响重金属离子的环境行为。然而，对于络合剂的存在是否会由于重金属暴露而改变水平基因转移，人们知之甚少。本研究旨在通过研究一种典型的络合剂乙二胺四乙酸（EDTA）对一系列重金属离子诱导的质粒介导的 ARGs 共轭转移的影响来填补这一空白。在环境相关浓度（0.64 mg/L）的金属离子下，所有测试的金属离子（Mg、Ca、Co、Pb、Ni、Cu 和 Fe）都促进了 ARGs 的共轭转移，而在相对较高的浓度（3.20 mg/L）下则观察到抑制作用。相比之下，EDTA（0.64 mg/L）缓解了金属离子对 ARGs 共轭转移的影响，共轭转移频率降低了 11%-66%。分子对接和动力学模拟表明，这归因于金属离子与细胞膜脂质的更强结合。在金属-EDTA 暴露下，与金属离子暴露相比，与氧化应激反应、细胞膜通透性、细胞间接触、能量驱动力、动员和质粒转移通道相关的基因表达受到抑制。本研究为络合剂对游离金属离子诱导的 ARGs 转移的缓解机制提供了新的见解。
