Sesamin and sesamolin rescues Caenorhabditis elegans from Pseudomonas aeruginosa infection through the attenuation of quorum sensing regulated virulence factors.

Pseudomonas aeruginosa is an opportunistic pathogen emerging as a public health threat owing to their multidrug resistance profiles. The quorum sensing systems of P. aeruginosa play a pivotal role in the regulation of virulence and act as the target for the development of alternative therapeutics. The study discussed about anti-quorum sensing and antibiofilm properties of lignans (sesamin and sesamolin) found in Sesamum indicum (L.) against P. aeruginosa. The effect of lignans, sesamin and sesamolin on LasR/RhlR mediated virulence factor production, biofilm formation and bacterial motility were studied. To elucidate the mechanism of action of lignans on QS pathways, QS gene expression and in depth in silico analysis were performed. Both the lignans exerted anti-quorum sensing activity at 75 μg/ml without affecting the growth of bacteria. SA and SO exhibited decreased production of virulence factors such as pyocyanin, proteases, elastase and chitinase. The important biofilm constituents of P. aeruginosa including alginate, exopolysaccharides and rhamnolipids were strongly affected by the lignans. Likewise, plausible mechanism of action of lignans were determined through the down regulation of QS regulated gene expression, molecular docking and molecular simulation studies. The in vitro analysis was supported by C. elegans infection model. SA and SO rescued pre-infected worms within 8 days of post infection and reduced the colonization of bacteria inside the intestine due to the anti-infective properties of lignans. The lignans exhibited profound action on Las pathway rather than Rhl which was elucidated through in vitro and in silico assays. In silico pharmacokinetic analysis portrayed the opportunities to employ ligands as potential therapeutics for human use. The deep insights into the anti-QS, anti-biofilm and mechanism of action of lignans can contribute to the development of novel anti-infectives against pseuodmonal infections.