title: Cranberry-derived proanthocyanidins impair virulence and inhibit quorum sensing of Pseudomonas aeruginosa.
abstract: Bacteria have evolved multiple strategies for causing infections that include producing virulence factors, undertaking motility, developing biofilms, and invading host cells. N-acylhomoserine lactone (AHL)-mediated quorum sensing (QS) tightly regulates the expression of multiple virulence factors in the opportunistic pathogenic bacterium Pseudomonas aeruginosa. Thus, inhibiting QS could lead to health benefits. In this study, we demonstrate an anti-virulence activity of a cranberry extract rich in proanthocyanidins (cerPAC) against P. aeruginosa in the model host Drosophila melanogaster and show this is mediated by QS interference. cerPAC reduced the production of QS-regulated virulence determinants and protected D. melanogaster from fatal infection by P. aeruginosa PA14. Quantification of AHL production using liquid chromatography-mass spectrometry confirmed that cerPAC effectively reduced the level of AHLs produced by the bacteria. Furthermore, monitoring QS signaling gene expression revealed that AHL synthases LasI/RhlI and QS transcriptional regulators LasR/RhlR genes were inhibited and antagonized, respectively, by cerPAC. Molecular docking studies suggest that cranberry-derived proanthocyanidin binds to QS transcriptional regulators, mainly interacting with their ligand binding sites. These findings provide insights into the underlying mechanisms of action of a cerPAC to restrict the virulence of P. aeruginosa and can have implications in the development of alternative approaches to control infections.
authors: Department of Chemical Engineering, McGill University, 3610 University Street, Montreal, Quebec, Canada.
authors: Vimal B
authors: VB
authors: Maisuria
authors: INRS-Institut Armand-Frappier, 531 boul. des Prairies, Laval, Québec, Canada.
authors: Yossef Lopez-de
authors: YL
authors: Los Santos
authors: Department of Chemical Engineering, McGill University, 3610 University Street, Montreal, Quebec, Canada.
authors: Nathalie
authors: N
authors: Tufenkji
authors: INRS-Institut Armand-Frappier, 531 boul. des Prairies, Laval, Québec, Canada.
authors: Eric
authors: E
authors: Déziel
mesh_terms: D054742:Acyl-Butyrolactones / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology; D004331:Drosophila melanogaster / Q000382:microbiology; D008297:Male; D062105:Molecular Docking Simulation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D044945:Proanthocyanidins / Q000302:isolation & purification / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D053038:Quorum Sensing / Q000187:drug effects; D015534:Trans-Activators / Q000737:chemistry / Q000502:physiology; D029799:Vaccinium macrocarpon / Q000737:chemistry*; D014774:Virulence / Q000187:drug effects
chemical_list: D054742:Acyl-Butyrolactones; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C081237:LasI protein, Pseudomonas aeruginosa; C080365:LasR protein, Pseudomonas aeruginosa; D010936:Plant Extracts; D044945:Proanthocyanidins; D015534:Trans-Activators