Transcriptomic analysis suggests the inhibition of DNA damage repair in green alga Raphidocelis subcapitata exposed to roxithromycin

Macrolide antibiotics are common contaminants in the aquatic environment. They are toxic to a wide range of primary producers, inhibiting the algal growth and further hindering the delivery of several ecosystem services. Yet the molecular mechanisms of macrolides in algae remain undetermined. The objectives of this study were therefore to: 1. evaluate whether macrolides at the environmentally relevant level inhibit the growth of algae; and 2. test the hypothesis that macrolides bind to ribosome and inhibit protein translocation in algae, as it does in bacteria. In this study, transcriptomic analysis was applied to elucidate the toxicological mechanism in a model green alga Raphidocelis subcapitata treated with 5 and 90 μg L⁻¹ of a typical macrolide roxithromycin (ROX). While exposure to ROX at 5 μg L⁻¹ for 7 days did not affect algal growth and the transciptome, ROX at 90 μg L⁻¹ resulted in 45% growth inhibition and 2306 (983 up- and 1323 down-regulated) DEGs, which were primarily enriched in the metabolism of energy, lipid, vitamins, and DNA replication and repair pathways. Nevertheless, genes involved in pathways in relation to translation and protein translocation and processing were dysregulated. Surprisingly, we found that genes involved in the base excision repair process were mostly repressed, suggesting that ROX may be genotoxic and cause DNA damage in R. subcapitata. Taken together, ROX was unlikely to pose a threat to green algae in the environment and the mode of action of macrolides in bacteria may not be directly extrapolated to green algae.