水体汞生物甲基化受喹诺酮类抗生素胁迫的细胞C1代谢通路

In recent years, there is an increasing interest in the environmental behaviors of antibiotics and their resistance, while bacterial methylation of mercury has long been a great concern for decades. As a most ubiquitous class of antibiotics, three quinolones are set as model drugs in this study. Under antibiotic stress of quinolones, the hormesis, i.e. a favorable and resistant response to low exposure to mixed drugs, is expected in typical mercury-methylating bacteria of Geobacter sulfurreducens PCA and Desulfovibrio desulphuricans ND132. Targeting at key metabolites regulating the evolution and transfer of methyl groups (one-carbon, C1 units) to mercury, the influencing pathways of quinolones will be revealed in those two iron and sulfate-reducing strains. At the sediment-water interface, where bacterial mercury methylation is actively involved, the dosage effect of different quinolones is to be investigated by profiling the metabolic response at cellular and molecular levels. Particularly upon prolonged exposure of low-concentration drug mixtures, the persistent effect of quinolones is to be elucidated by metabolite indicators, whilst the impact of eco-environmental variations is to be uncovered by distribution, speciation and methylation of mercury. From a new perspective of metabolomics, the metabolic C1 mechanism of bacterial mercury methylation is to be provided in antibiotic-mercury complex.

水环境中抗生素及其抗性的微生态效应是当前的研究热点，其对汞生物甲基化的影响也备受关注。本研究针对水体高频检出的3种喹诺酮类抗生素的胁迫作用，提出“低浓度、混合抗生素对汞生物甲基化的促进和抗性效应”假说。在汞生物甲基化过程活跃的沉积物-水界面，以典型汞甲基化微生物Geobacter sulphurreducens PCA和Desulfovibrio desulphuricans ND132为研究对象，阐释铁/硫酸盐还原菌调控甲基生成和传递的一碳（C1）代谢通路。在抗生素-汞复合污染水体中，分析微生物受不同浓度、种类抗生素胁迫的关键代谢物组学差异。重点在低浓度、长时间、混合抗生素暴露条件下，筛选抗性诱导的细胞代谢标志物。对比铁/硫酸盐和天然腐殖酸两类显著环境因子对细胞代谢的影响水平，耦合汞和甲基汞的赋存形态与转化效率，从代谢组学的新角度探讨抗生素对汞生物甲基化的促进和抗性机制。

近年来，抗生素污染在水环境中的毒性作用和降解机制成为热点。然而，有关抗生素在水环境中的微生物生态学效应研究较少。本研究验证了“低浓度、混合抗生素对汞生物甲基化的促进效应”假说。研究以典型汞甲基化微生物Geobacter sulphurreducens PCA和Geobacter metallireducens GS-15为研究对象。结果表明，在环境污染浓度（5-50 μg/L）下，洛美沙星对GS-15菌生长具有抑制作用，且呈现浓度梯度效应。同时，洛美沙星母体更易被GS-15菌生物降解，氧化、羟基化和脱氯等为抗生素降解的主要途径。在较低的污染浓度（5 μg/L）下，洛美沙星对GS-15汞生物甲基化具有促进作用。汞甲基化微生物的单细胞活性升高是促进甲基汞生成的潜在机理。洛美沙星诱导的毒性兴奋效应和较高的细胞蛋白活性，可以有效地促进GS-15菌单细胞的汞生物甲基化能力。作为显著的环境影响因子，腐殖酸对甲基汞生成具有剂量效应，且呈现菌种间差异。在环境污染浓度（10 μg/L）的单种抗生素（氧氟沙星）胁迫作用下，汞甲基化微生物（PCA菌）胞内代谢通路发生显著变化。五种混合抗生素暴露诱导出更多具有组学差异的胞内代谢物。本研究为解决抗生素-汞复合污染及相关的水环境安全问题，提供理论指导。