Abstract：
Erythromycin (ERY) is a typical macrolide antibiotic with large production and extensive use on a global scale. Detection of ERY in both freshwaters and coaster seawaters, as well as relatively high ecotoxicity of ERY have been documented. Notably, hormesis has been reported on several freshwater algae under ERY stress, where growth was promoted at relatively lower exposures but inhibited at higher treatment levels. On the contrary, there is limited information of ERY toxicity in marine algae, hampering the risk assessment on ERY in the coaster waters. The presence of hormesis may challenge the current concept of dose-response adopted in chemical risk assessment. Whether and how exposure to ERY can induce dose-dependent toxicity in marine algae remain virtually unknown, especially at environmentally relevant concentrations. The present study used a model marine diatom Thalassiosira weissflogii (T. weissflogii) to reveal its toxicological responses to ERY at different biological levels and decipher the underlying mechanisms. Assessment of multiple apical endpoints shows an evident growth promotion following ERY exposure at an environmentally relevant concentration (1 µg/L), associated with increased contents reactive oxygen species (ROS) and chlorophyll-a (Chl-a), activated signaling pathways related to ribosome biosynthesis and translation, and production of total soluble protein. By contrast, growth inhibition in the 750 and 2500 µg/L treatments was attributed to reduced viability, increased ROS formation, reduced content of total soluble protein, inhibited photosynthesis, and perturbed signaling pathways involved in xenobiotic metabolism, ribosome, metabolism of amino acid, and nitrogen metabolism. Measurements of multiple apical endpoints coupled with de novo transcriptomics analysis applied in the present study, a systems biology approach, can generate detailed mechanistic information of chemical toxicity including dose-response and species sensitivity difference used in environmental risk assessment.
摘要：
红霉素（ERY）是一种典型的大环内酯类抗生素，在全球范围内产量大，用途广泛。在淡水和过山车海水中检测ERY，以及相对较高的生态毒性的ERY已被记录。值得注意的是,据报道，在ERY压力下，几种淡水藻类的hormesis，其中生长在相对较低的暴露下得到促进，但在较高的处理水平下受到抑制。相反,海洋藻类的ERY毒性信息有限，阻碍了过山车水域ERY的风险评估。hormesis的存在可能会挑战当前在化学风险评估中采用的剂量反应概念。暴露于ERY是否以及如何在海藻中诱导剂量依赖性毒性仍然未知，特别是在环境相关的浓度。本研究使用了海洋硅藻模型（T.weissflogii）以揭示其在不同生物学水平上对ERY的毒理学反应，并破译其潜在机制。对多个顶端终点的评估显示，在环境相关浓度（1µg/L）的ERY暴露后，明显的生长促进，与活性氧（ROS）和叶绿素a（Chl-a）含量增加有关，激活与核糖体生物合成和翻译相关的信号通路，和总可溶性蛋白质的生产。相比之下,750和2500µg/L处理中的生长抑制归因于生存力降低，ROS形成增加，总可溶性蛋白质含量降低，抑制光合作用，以及参与异源生物代谢的信号通路，核糖体,氨基酸代谢，和氮代谢。本研究中应用的多个顶端端点的测量与从头转录组学分析相结合，系统生物学方法，可以生成详细的化学毒性机制信息，包括用于环境风险评估的剂量反应和物种敏感性差异。
