Deciphering the role of coumarin as a novel quorum sensing inhibitor suppressing virulence phenotypes in bacterial pathogens

Abstract

The rapid unchecked rise in antibiotic resistance over the last few decades has led to an increased focus on the need for alternative therapeutic strategies for the treatment and clinical management of microbial infections. In particular, small molecules that can suppress microbial virulence systems independent of any impact on growth are receiving increased attention. Quorum sensing (QS) is a cell-to-cell signalling communication system that controls the virulence behaviour of a broad spectrum of bacterial pathogens. QS systems have been proposed as an effective target, particularly as they control biofilm formation in pathogens, a key driver of antibiotic ineffectiveness. In this study, we identified coumarin, a natural plant phenolic compound, as a novel QS inhibitor, with potent anti-virulence activity in a broad spectrum of pathogens. Using a range of biosensor systems, coumarin was active against short, medium and long chain N-acyl-homoserine lactones, independent of any effect on growth. To determine if this suppression was linked to anti-virulence activity, key virulence systems were studied in the nosocomial pathogen Pseudomonas aeruginosa. Consistent with suppression of QS, coumarin inhibited biofilm, the production of phenazines and swarming motility in this organism potentially linked to reduced expression of the rhlI and pqsA quorum sensing genes. Furthermore, coumarin significantly inhibited biofilm formation and protease activity in other bacterial pathogens and inhibited bioluminescence in Aliivibrio fischeri. In light of these findings, coumarin would appear to have potential as a novel quorum sensing inhibitor with a broad spectrum of action.

Anti-Biofilm and Antivirulence Activities of Metabolites from Plectosphaerella cucumerina against Pseudomonas aeruginosa

“…In this study, mellein showed no antivirulence or anti-biofilm capacities. Recently, coumarin was reported to possess antivirulence and anti-biofilm capacities against P. aeruginosa (Gutiérrez-Barranquero et al, 2015). Citreoisocoumarin, one coumarin analog, showed no antivirulence or anti-biofilm capacities in this study.…”

Anti-quorum sensing activity of Forsythia suspense on Chromobacterium violaceum and Pseudomonas aeruginosa

“…[14] Briefly, 50 μL of cell-free supernatant of FSE-treated and FSE-untreated P. aeruginosa was separately added in LB solid medium containing 5% skim milk have holes and incubated at 30°C for 18 h. The circle of casein hydrolysis was detected.…”

Identification of Ellagic Acid Rhamnoside as a Bioactive Component of a Complex Botanical Extract with Anti-biofilm Activity

“…As phenol and catechol are key structural components of EA ( Figures 1 , 2 ) and other phenolic compounds have shown anti-biofilm and anti-quorum sensing activity (Cowan, 1999; Brielmann, 2010; Gutierrez-Barranquero et al, 2015; Onsare and Arora, 2015; Zhou et al, 2015; Tsou et al, 2016), they were chosen as targets to determine the structural elements of the EA core required for bioactivity. Phenol and catechol containing compounds are widely observed in plant natural products (Cowan, 1999; Brielmann, 2010), suggesting that they may occur within R. ulmifolius .…”