Integrative analyses of transcriptomics and metabolomics in Raphidocelis subcapitata treated with clarithromycin

As a macrolide antibiotic, clarithromycin (CLA) has a high detection rate in surface water and sewage treatment plant effluents worldwide, posing a considerably high ecological risk to aquatic ecosystem. However, algal transcriptome and metabolome in response to CLA remains largely unknown. In this study, a model alga Raphidocelis subcapitata (R. subcapitata), was exposed to CLA at the concentrations of 0, 3, 10, and 15 μg L^-1. Transcriptomic analysis was performed for all the treatment groups, whereas metabolomics was merely applied to 0, 3, and 10 μg L^-1 groups because of the limited amount of algal biomass. After 7 d cultivation, the growth of R. subcapitata was significantly hindered at the concentrations above 10 μg L^-1. A total of 115, 1833, 2911 genes were differentially expressed in 3, 10, and 15 μg L^-1 groups, respectively; meanwhile, 134 and 84 differentially accumulated metabolites (DAMs) were found in the 3 and 10 μg L^-1 groups. Specifically, expression levels of DEGs and DAMs related to xenobiotic metabolism, electron transport and energy synthesis were dysregulated, leading to the produced reactive oxygen species (ROS). To confront the CLA-induced injury, the biosynthesis of unsaturated fatty acids and carotenoids of R. subcapitata in 3 μg L^-1 were up-regulated; although the photosynthesis was up-regulated in both 10 μg L^-1 and 15 μg L^-1 groups, the energy synthesis and the ability to resist ROS in these two groups were down-regulated. Overall, this study shed light on the mechanism underlying the inhibitory effects of macrolide antibiotics in algae.