Natural compounds targeting pyocyanin and quorum sensing in Pseudomonas aeruginosa

Abstract : Pseudomonas aeruginosa is a Gram-negative bacterium representing a serious threat for individuals and public health. This opportunistic human pathogen is associated with diverse range of infections that are commonly difficult to eradicate successfully and is considered one of the important resistant bacteria to conventional antibiotic therapy at a global level. World Health Organization identified P. aeruginosa as a critical priority for which innovative new treatments are urgently needed. This study aims to attenuate bacterial virulence through interference with the expression or activity of virulence factors in P. aeruginosa. Pyocyanin is a blue redox-active toxin factor, produced by P. aeruginosa and strongly-controlled by the pqs quorum sensing (QS) system that uses alkyquinolone (AQ) derived signal molecules. A library of novel natural extracts and compounds from terrestrial plants and algae were screened on a P. aeruginosa PAO1 strain for their effects on viability, pyocyanin and QS signaling molecules production. A number of extracts and compounds tested showed significant inhibition of the targeted virulence factor. For instance, one of the selected extract (DM1) inhibited pyocyanin production in a dose-dependent manner and showed strongest activity (>80% reduction) when used at a concentration of 100 µg/ml. Accordingly, we observed a reduction on AQ production. The selected extracts and compounds will be further screened for other virulence factors production and they will be assayed alone or in combination with conventional antibiotics on a large collection of clinical strains of P. aeruginosa.