Transcriptome Analysis Reveals the Mechanism of Y0-C10-HSL on Biofilm Formation and Motility of Pseudomonas aeruginosa

<b>Background:</b><i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>) is a type of pathogen that takes advantage of opportunities to infect and form biofilm during infection. Inhibiting biofilm formation is a promising approach for the treatment of biofilm-related infections. <b>Methods:</b> Here, Y0-C10-HSL (N-cyclopentyl-n-decanamide) was designed, synthesized, and tested for its effect on biofilm formation, motility, and the <i>Caenorhabditis elegans</i> (<i>C. elegans</i>) survival assay. In addition, the molecular mechanism of Y0-C10-HSL on <i>P. aeruginosa</i> biofilm formation was explored using transcriptome analysis. <b>Results:</b> At a concentration of 200 μmol/L Y0-C10-HSL, biofilm and exopolysaccharides were decreased by 38.5% and 29.3%, respectively; Y0-C10-HSL effectively dispersed the pre-formed biofilm and inhibited the motility ability of <i>P. aeruginosa</i>; and the <i>C. elegans</i> survival assay showed that Y0-C10-HSL was safe and provided protection to <i>C. elegans</i> against <i>P. aeruginosa</i> infection (the survival rates of <i>C. elegans</i> were higher than 74% and increased by 39%, 35.1%, and 47.5%, respectively, when treated with 200 μmol/L Y0-C10-HSL at 24, 48, and 80 h). Transcriptome analysis showed that 585 differentially expressed genes (DEGs) were found after treatment with 200 μmol/L Y0-C10-HSL, including 254 up-regulated DEGs and 331 down-regulated DEGs. The genes involved in the quorum sensing system and biofilm formation were down-regulated. <b>Conclusions:</b> Y0-C10-HSL inhibited the biofilm formation and dispersed the pre-formed biofilm of <i>P. aeruginosa</i> through down-regulated genes related to quorum sensing pathways and biofilm formation. These findings provide a theoretical foundation for the treatment and prevention of antibiotic resistance in clinical and environmental microorganisms such as <i>P. aeruginosa</i>.