Myricetin as a potential therapeutic agent against <i>Pseudomonas aeruginosa</i> : inhibition of biofilm formation, quorum sensing, and virulence factor production

Multidrug-resistant pathogenic bacteria, particularly Pseudomonas aeruginosa (P. aeruginosa), pose a significant threat to human health. Despite the huge persistence of antibiotics, there remains a lack of effective natural compounds capable of simultaneously disrupting quorum sensing (QS), biofilm formation, and virulence in this pathogen. This study aimed to investigate the inhibitory potential of myricetin against P. aeruginosa focusing on its ability to interfere with QS-regulated virulence traits. Antibacterial, antibiofilm, anti-QS, and virulence factor activities were evaluated using crystal violet biofilm formation and QS-regulated virulence factor inhibition assays (e.g. pyocyanin, rhamnolipid, protease, and exopolysaccharides). The minimum inhibitory concentration (MIC) required to inhibit visible bacterial growth was 0.97 mg/mL. Additionally, the minimum biofilm inhibitory concentration of 50 (MBIC50) was recorded at the MIC value. Myricetin showed a significant inhibitory effect against biofilm formation by suppressing bacterial hydrophobicity, aggregation, and swarming motility. Furthermore, myricetin significantly reduced the production of pyocyanin, rhamnolipid, protease, and exopolysaccharides. The myricetin effectively impeded QS mechanisms as evidenced by a significant reduction in the production of acyl homoserine lactone and violacein pigment, both qualitatively and quantitatively. Gene expression analysis exhibited a significant downregulation of LasI/R and RhlI/R genes, further enhancing the myricetin role in QS inhibition. Collectively, these findings demonstrate that myricetin effectively interferes with QS-mediated virulence mechanisms in P. aeruginosa, supporting its potential as a promising lead compound for developing anti-virulence strategies.