Perillaldehyde mitigates virulence factors and biofilm formation of Pseudomonas aeruginosa clinical isolates, by acting on the quorum sensing mechanism in vitro.

Aim: The incidence of biofilm linked catheter‐associated urinary tract infections is increasing worldwide and Pseudomonas aeruginosa is one of the major causes. Perillaldehyde (PLD): as a natural, widely used flavouring agent, has been reported to possess various pharmacological properties. We hypothesized that PLD can inhibit biofilm formation and virulence factor (VF) production by P. aeruginosa by hampering the quorum sensing (QS) system(s). Methods and Results: Minimum inhibitory concentration (MIC) of PLD was assessed for standard strain and two multi‐drug resistant catheter isolates of P. aeruginosa utilizing the microdilution method. Microtiter plate assay, crystal violet staining and scanning electron microscopy were used to evaluate the biofilm inhibition property. CFU was utilized to assess the antifouling property of PLD. Detection of VFs and expression analysis of virulence determinants were applied to investigate the anti‐virulence activity. Gene expression and molecular docking studies were also executed to explore the QS inhibition and binding of PLD with QS receptors. In the present study, PLD has significantly inhibited biofilm formation and antivirulence activity at sub‐MIC levels (2.5 and 3.5 mM) in all the tested strains. In addition, molecular docking studies revealed a significant affinity towards QS receptors. Discussions: Perillaldehyde, being a non‐toxic food flavouring agent, significantly inhibited biofilm formation and exhibited antifouling property. PLD exhibited significantly reduced levels of VFs (p < 0.001) and their respective genetic determinants (p < 0.001). Gene expression analysis and molecular docking studies confirmed the interactions of PLD to the QS receptors, indicating the plausible mechanism for the anti‐virulence property. Significance and Impact of Study: This study identified the anti‐virulence potential of PLD and provided mechanistic insights. PLD can be a suitable, non‐toxic candidate for countering biofilms and associated pathogens, contributing to the prevention of biofilm‐associated nosocomial infections. [ABSTRACT FROM AUTHOR]