Integrating multi-omics analysis unveils the key mechanisms of PQS-enhanced Algicidal activity in Enterobacter...

Quorum sensing, as a pivotal bacterial signaling pathway, exhibits substantial potential for regulating algicidal activity. This study pioneers the integration of multi-omics analyses (transcriptomics, proteomics, metabolomics) with phenotypic profiling to systematically unravel the molecular mechanisms underlying Pseudomonas Quinolone Signal (2-heptyl-3-hydroxy-4(1H)-quinolinone, PQS)-enhanced algicidal activity in Enterobacter hormaechei F2. Co-cultivation with PQS triggered marked reductions in algal biomass and chlorophyll-a levels, outperforming traditional approaches. Fourier-transform infrared spectroscopy (FTIR) revealed PQS-induced metabolic disruption and membrane degradation in algal cells. Transcriptomic profiling identified novel regulatory hubs, including upregulated glycolysis (tktA, transketolase), fatty acid degradation (fadE, acyl-CoA dehydrogenase), and chemotaxis (malE, maltose-binding protein) pathways. Proteomics confirmed PQS-driven enrichment of terpenoid precursors, notably DXS synthase (1-deoxy-D-xylulose-5-phosphate synthase), and quorum sensing effectors. Metabolomics highlighted amino acid derivatives (e.g., L-glutamate) and heterocyclic antibiotics as dominant algicidal metabolites. Crucially, multi-omics integration delineated a core network of 46 key nodes (e.g., ribose transporter rbsB, L-glutamate) coordinating energy metabolism, motility, and algicide synthesis. Fatty acid degradation enzymes (e.g., FadE) and flagellar assembly regulators (e.g., FlgK) emerged as previously unrecognized targets, with PQS significantly enhancing bacterial swarming motility (p < 0.01) and biofilm formation. These findings establish the first mechanistic framework linking PQS signaling to algicidal process, demonstrating its role in synchronizing metabolic flux toward terpenoid synthesis while optimizing bacterial-algal interactions. Key pathways-including chemotaxis (malE) and terpenoid biosynthesis (DXS synthase)-provide actionable targets for engineering bioaugmented consortia or precision algicidal formulations. This work advances quorum sensing-driven strategies for sustainable harmful algal bloom (HAB) mitigation, offering scalable solutions for aquaculture and eutrophic water remediation with minimal ecological disruption. By bridging molecular mechanisms to field applications, the study underscores the translational potential of this approach in global water security initiatives.