Deciphering the joint intracellular and extracellular regulatory strategies of toxigenic Microcystis to achieve intraspecific competitive advantage: An integrated multi-omics analysis with novel allelochemicals identified.

Global increase in Microcystis-dominated cyanobacterial blooms (MCBs) severely threatens ecological and human health. Intraspecific interaction between microcystin (MC)-producing (MC) Microcystis and co-existing MC-free (MC) Microcystis influences the relative abundance of MCMicrocystis, ultimately determining the toxicity and hazard of MCBs. However, specific allelochemicals driving this interaction and underlying molecular mechanisms remain unclear. This study confirmed that intraspecific interaction promoted the competitive advantage of MCMicrocystis over MCMicrocystis and unveiled the joint intracellular and extracellular regulatory strategies of MCMicrocystis based on proteomics-metabolomics analyses and biochemical validation. Intracellularly, MCMicrocystis enhanced pentose phosphate pathway and lipid and fatty acid biosynthesis to maintain cellular functions and membrane stability, but inhibited glycolysis, tricarboxylic acid cycle, and protein biosynthesis to optimize energy utilization for growth and proliferation. Extracellularly, MCMicrocystis released allelochemicals, including cytidine diphosphate-diacylglycerol and N-acyl-homoserine lactones, to inhibit MCMicrocystis growth by 13.53% and 16.39%, respectively, thereby achieving its competitive advantage. In contrast, MCMicrocystis exhibited the suppressed photosynthesis and oxidative phosphorylation, imbalanced anti-inflammatory responses, nucleic acid degradation, and membrane damage, resulting in its competitive disadvantage in co-culture. These findings provide new insights into the competitive dynamics between MC and MCMicrocystis, and their involved implications for aquatic ecosystem health.