Indole competitively inhibits quorum sensing and triggers oxidative stress to suppress Microcystis blooms

The proliferation of cyanobacterial blooms poses a significant threat to aquatic ecosystems and drinking water safety. Traditional control strategies mainly focus on environmental factors and overlook microbial communication networks. This study systematically elucidated the quorum sensing (QS) system in Microcystis aeruginosa and identified a previously unknown QS signaling molecule N-carboxy-C₁₀-homoserine lactone (N-carboxy-C₁₀-HSL), and its homologous synthase and receptor in the genome for MaeI/MaeR through ultra-high resolution mass spectrometry and genomics methods. These findings provide precise targets for disrupting the QS regulation of M. aeruginosa. As a biocompatible quorum quencher, indole achieved a 95.3 % inhibition rate within 14 days at 0.55 mM. Mechanistically, sub-inhibitory indole (0.07 mM) down-regulates the transcripts of maeI and maeR by 31 % and 38 %, suppressing QS regulation, while higher doses (EC₅₀) induced membrane perturbation and reactive oxygen species (ROS)‑mediated oxidative stress, as evidenced by an 88.6 % decrease in PSII quantum efficiency and a 14.6‑fold increase in malondialdehyde (MDA) levels. Molecular docking confirmed its unique competitive inhibition of AHL MaeR binding through hydrogen bonding (-4.8 kcal/mol) with ASP101 (A). Unlike traditional algaecides, this method significantly reduces the production of microcystin-LR and ecological risks by targeted downregulation of maeI/maeR. These findings indicate that quorum quenching is a promising sustainable algal bloom mitigation strategy that can protect aquatic ecosystems by simultaneously controlling algal proliferation and toxin production.