A dual-action strategy of propenyl guaethol: pilY-mediated biofilm inhibition and augmenting aminoglycoside antibiofilm activity against <i>Pseudomonas aeruginosa</i> through <i>in vitro</i> and <i>in silico</i> studies

Flavoring compounds are natural or synthetic substances that enhance the food flavor. Research studies have demonstrated that flavoring compounds may have biological activities. In food industry, <i>P. aeruginosa</i> dominates spoilage and contamination of food products. Human exposure to <i>P. aeruginosa</i> may lead to serious infections. <i>P. aeruginosa</i> forms complex biofilms with extracellular slime matrix, providing protection against antimicrobial agents. The present study investigates the role of a flavouring food additive, propenyl guaethol (PG) against <i>Pseudomonas aeruginosa</i> biofilms. Our results demonstrate a significant impact of PG on biofilm forming ability, bacterial attachment, and motility phenotypes. The polystyrene tube assay demonstrates notable inhibition of biofilm formation by <i>P. aeruginosa</i> at 50 and 25 µg/ml (<i>p</i> < 0.01). PG showed marked inhibition of biofilms in combination with gentamicin, kanamycin, and streptomycin. Additionally, PG inhibits twitching, swarming, and swimming motility of <i>P. aeruginosa</i> (<i>p</i> < 0.01). Scanning electron microscopy, fluorescent microscopy, and light microscopy showed thinner biofilms with low exopolysaccharide matrix (EPS) in the presence of PG. Moreover, the role of PG was also evaluated using molecular docking and molecular dynamics simulation to understand the interaction of PG with bacterial type-IV pili subunit, PilY1. PG showed favourable interactions and stable complex formation with type-IV pili subunit (PilY1). The present study highlights the antibiofilm properties of PG, suggesting its potential as a biofilm control flavoring compound.