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

Highlights: • Exposure to tylosin at 3 μg/L and 400 μg/L inhibited growth of R. subcapitata. • Signaling pathways related to xenobiotic metabolism were inhibited. • Molecular pathways of photosynthesis and DNA replication-repair were suppressed. • Energy metabolism in both tylosin treatments was impaired. • Photosynthesis was identified as the most sensitive signaling target for tylosin. 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⁻¹ 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⁻¹ 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⁻¹ 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.