Multistage defense response of microalgae exposed to pharmaceuticals in wastewater

Recently, the use of microalgae for bioremediation of pharmaceuticals (PhAs) has attracted increasing interest. However, most studies focused more on microalgae removal performance, its defensive response to the PhAs during wastewater treatment remains unexplored. Herein, microalgal three defensive systems have been investigated in synthetic wastewater, with six PhAs as the typical drug. Results show that PhAs could bind to EPS, and this action in turn could help to alleviate the direct toxicity of PhAs to microalgae. Subsequently, the physiological analyses revealed the increase of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities, potentially reducing the oxidative stress induced by PhAs. Furthermore, the enzyme activities of cytochrome P450 (CYP450) and glutathione-S-transferase (GST) were significantly upregulated after exposure to SMX, CIP and BPA, followed by a significant decrease in biodegradation rates after the addition of CYP450 inhibitors, suggesting that the biotransformation and detoxification of PhAs occurred. Meanwhile, molecular docking further revealed that CYP450 could bind with PhAs via hydrogen bond and hydrophobic interaction, which proved their abilities to be metabolized and form transformation products in microalgae. These findings provide an advancing understanding of microalgae technologies to improve the treatment of wastewater contaminated with PhAs. This study comprehensively unravels the defense mechanisms of microalgae against PhAs in wastewater. The result demonstrates that the defense of microalgae under PhAs is a multistage process involving an extracellular polymeric substance (EPS), intracellular antioxidant system, and detoxifying enzymes.