Role of fatty acids in modulating quorum sensing in Pseudomonas aeruginosa and Chromobacterium violaceum: an integrated experimental and computational analysis

Abstract

The broad-spectrum antibacterial capabilities of fatty acids (FAs) and their reduced propensity to promote resistance have rendered as a promising substitute for conventional antibiotics. The structural significance of fatty acid production with the other lipids is a major energy source, and signal transduction has drawn a great deal of research attention to these biomolecules. Saturated and monounsaturated fatty acids reduce virulence by preventing harmful opportunistic bacteria like Pseudomonas aeruginosa and Chromobacterium violaceum from activating their quorum sensing (QS) systems. In this finding, the fatty acids capric acid, caprylic acid, and monoelaidin were selected to evaluate their anti-QS activity against the C. violaceum and P. aeruginosa. At the minimum inhibitory concentration (MIC) and sub-MIC concentration of the three fatty acids, the virulence factor production of both the bacteria was quantified. The virulence factors like EPS, biofilm quantification and visualization, and motility assays were inhibited in the dose-dependent manner (MIC and sub-MIC) for both the organisms whereas this pattern was followed in the pyocyanin, pyoverdine, rhamnolipid, protease of P. aeruginosa and the violacein, and chitinase of C. violaceum. In all these biochemical assays, the capric acid could effectively reduce the production and further validated at gene expression level by RT-qPCR. The study on the gene expression for all these virulence factors reveals that the capric acid inhibited the growth of both the organisms in a higher fold than the caprylic and monoelaidin. The in silico approach of structural validation for the binding of ligands with the proteins in the QS circuit was studied by molecular docking in Schrodinger software. The Las I and Las R in P. aeruginosa and the CviR of C. violaceum protein structures were docked with the selected three fatty acids. The capric acid binds to the pocket with the highest binding score of all the proteins than the caprylic and monoelaidin fatty acids. Thus, capric acid proves to be the therapeutic biomolecule for the anti-QS activity of opportunistic bacteria.

Graphical Abstract