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通过转录组和代谢组的综合分析揭示雨生红球藻中海他霉素毒性:光合作用和 DNA 复制偶联修复。

Tylosin toxicity in the alga Raphidocelis subcapitata revealed by integrated analyses of transcriptome and metabolome: Photosynthesis and DNA replication-coupled repair.

机构信息

Shaanxi Key Laboratory of Earth Surface System and Environmental Carrying Capacity, College of Urban and Environmental Sciences, Northwest University, Xi'an 710127, China.

Shaanxi Key Laboratory of Earth Surface System and Environmental Carrying Capacity, College of Urban and Environmental Sciences, Northwest University, Xi'an 710127, China.

出版信息

Aquat Toxicol. 2021 Oct;239:105964. doi: 10.1016/j.aquatox.2021.105964. Epub 2021 Sep 9.

DOI:10.1016/j.aquatox.2021.105964
PMID:34534865
Abstract

Tylosin (TYN) is widely used in veterinary prophylactic as a macrolide and frequently detected in the surface water. Previous studies showed that exposure to TYN caused suppression of chlorophyll biosynthesis and inhibition of photosynthesis at the physiological level, associated with reduced growth performances in algae, but the molecular mechanisms remain unknown, especially at environmental exposure levels. The present study elucidated the underlying molecular mechanism(s) of TYN toxicity in a model green alga Raphidocelis subcapitata using approaches of transcriptomics and metabolomics. Following a 7-day exposure, algal growth performances were reduced by 26.3% and 58.3% in the 3 (an environmentally realistic level) and 400 μg L TYN treatment group, respectively. A total of 577 (99) and 5438 (180) differentially expressed genes (differentially accumulated metabolites) were identified in algae treated with 3 and 400 μg L TYN, respectively. Signaling pathways including photosynthesis - antenna protein, porphyrin and chlorophyll metabolism, carbon fixation in photosynthetic organisms, and DNA replication were altered in the 400 μg L TYN treatment, while photosynthesis and DNA replication were the shared pathways in both TYN treatments. The metabolomic data further suggest that molecular pathways related to photosynthesis, DNA replication-coupled repair and energy metabolism were impaired. Photosynthesis was identified as the most sensitive target of TYN toxicity in R. subcapitata, in contrast to protein synthesis inhibition caused by TYN in bacteria. This study provides novel mechanistic information of TYN toxicity in R. subcapitata.

摘要

泰乐菌素(TYN)作为一种大环内酯类抗生素,被广泛应用于兽医预防领域,常被检测到存在于地表水环境中。先前的研究表明,TYN 的暴露会抑制叶绿素的生物合成和光合作用,在生理水平上导致光合作用受到抑制,进而降低藻类的生长性能,但其中的分子机制尚不清楚,尤其是在环境暴露水平下。本研究采用转录组学和代谢组学的方法,阐明了 TYN 在模式绿藻莱茵衣藻中的毒性作用的潜在分子机制。经过 7 天的暴露,在 3(一个现实环境水平)和 400μg/L TYN 处理组中,藻类的生长性能分别降低了 26.3%和 58.3%。在分别用 3 和 400μg/L TYN 处理的藻类中,分别鉴定出 577(99)和 5438(180)个差异表达基因(差异积累代谢物)。在 400μg/L TYN 处理中,包括光合作用-天线蛋白、卟啉和叶绿素代谢、光合生物中的碳固定以及 DNA 复制在内的信号通路发生了改变,而在两种 TYN 处理中,光合作用和 DNA 复制是共同的通路。代谢组学数据进一步表明,与光合作用、与 DNA 复制相关的修复和能量代谢相关的分子途径受到了损害。与 TYN 在细菌中引起的蛋白质合成抑制不同,本研究表明,光合作用是 TYN 对莱茵衣藻毒性的最敏感靶标。这项研究为 TYN 在莱茵衣藻中的毒性作用提供了新的机制信息。

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