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

Abstract

Background: Pseudomonas aeruginosa (P. aeruginosa) 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. Methods: Here, Y0-C10-HSL (N-cyclopentyl-n-decanamide) was designed, synthesized, and tested for its effect on biofilm formation, motility, and the Caenorhabditis elegans (C. elegans) survival assay. In addition, the molecular mechanism of Y0-C10-HSL on P. aeruginosa biofilm formation was explored using transcriptome analysis. Results: 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 P. aeruginosa; and the C. elegans survival assay showed that Y0-C10-HSL was safe and provided protection to C. elegans against P. aeruginosa infection (the survival rates of C. elegans 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. Conclusion: Y0-C10-HSL inhibited the biofilm formation and dispersed the pre-formed biofilm of P. aeruginosa 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 P. aeruginosa.