title: Pseudomonas aeruginosa Biofilm Formation and Persistence, along with the Production of Quorum Sensing-Dependent Virulence Factors, Are Disrupted by a Triterpenoid Coumarate Ester Isolated from Dalbergia trichocarpa, a Tropical Legume.
abstract: Recently, extracts of Dalbergia trichocarpa bark have been shown to disrupt P. aeruginosa PAO1 quorum sensing (QS) mechanisms, which are key regulators of virulence factor expression and implicated in biofilm formation. One of the active compounds has been isolated and identified as oleanolic aldehyde coumarate (OALC), a novel bioactive compound that inhibits the formation of P. aeruginosa PAO1 biofilm and its maintenance as well as the expression of the las and rhl QS systems. Consequently, the production of QS-controlled virulence factors including, rhamnolipids, pyocyanin, elastase and extracellular polysaccharides as well as twitching and swarming motilities is reduced. Native acylhomoserine lactones (AHLs) production is inhibited by OALC but exogenous supply of AHLs does not restore the production of virulence factors by OALC-treated cultures, indicating that OALC exerts its effect beyond AHLs synthesis in the QS pathways. Further experiments provided a significant inhibition of the global virulence factor activator gacA by OALC. OALC disorganizes established biofilm structure and improves the bactericidal activity of tobramycin against biofilm-encapsulated PAO1 cells. Finally, a significant reduction of Caenorhabditis elegans paralysis was recorded when the worms were infected with OALC-pre-treated P. aeruginosa. Taken together, these results show that triterpenoid coumarate esters are suitable chemical backbones to target P. aeruginosa virulence mechanisms.
authors.affiliation: Laboratoire de Biotechnologie Végétale, Université Libre de Bruxelles, Gosselies, Belgium; Laboratoire de Formation et de Recherche en Biologie Médicale, Faculté de Médecine, Université d'Antananarivo, Antananarivo, Madagascar.
authors.forename: Tsiry
authors.initials: T
authors.lastname: Rasamiravaka
authors.affiliation: Laboratoire de Biotechnologie Végétale, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Olivier M
authors.initials: OM
authors.lastname: Vandeputte
authors.affiliation: Laboratoire de Pharmacognosie, de Bromatologie et de Nutrition Humaine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pottier
authors.affiliation: Laboratoire de Pharmacognosie, de Bromatologie et de Nutrition Humaine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Joelle
authors.initials: J
authors.lastname: Huet
authors.affiliation: Laboratoire de Biodiversité et de Biotechnologie, Institut Malgache de Recherches Appliquées, Antananarivo, Madagascar.
authors.forename: Christian
authors.initials: C
authors.lastname: Rabemanantsoa
authors.affiliation: Laboratoire de Biotechnologie Végétale, Université Libre de Bruxelles, Gosselies, Belgium; Laboratoire de Biochimie et de Chimie Appliquées, Université de Ouagadougou, Ouagadougou, Burkina Faso.
authors.forename: Martin
authors.initials: M
authors.lastname: Kiendrebeogo
authors.affiliation: Laboratoire de Formation et de Recherche en Biologie Médicale, Faculté de Médecine, Université d'Antananarivo, Antananarivo, Madagascar.
authors.forename: Abel
authors.initials: A
authors.lastname: Andriantsimahavandy
authors.affiliation: Laboratoire de Formation et de Recherche en Biologie Médicale, Faculté de Médecine, Université d'Antananarivo, Antananarivo, Madagascar.
authors.forename: Andry
authors.initials: A
authors.lastname: Rasamindrakotroka
authors.affiliation: Laboratoire de Pharmacognosie, de Bromatologie et de Nutrition Humaine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Stévigny
authors.affiliation: Laboratoire de Pharmacognosie, de Bromatologie et de Nutrition Humaine, Université Libre de Bruxelles, Brussels, Belgium; Service de Chimie Thérapeutique et de Pharmacognosie, Université de Mons, Mons, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Duez
authors.affiliation: Laboratoire de Biotechnologie Végétale, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Mondher
authors.initials: M
authors.lastname: El Jaziri
mesh_terms: D054742:Acyl-Butyrolactones / Q000378:metabolism; D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D017173:Caenorhabditis elegans / Q000187:drug effects; D003373:Coumaric Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D035782:Dalbergia / Q000737:chemistry*; D004357:Drug Synergism; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial; D009068:Movement / Q000187:drug effects; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D010243:Paralysis / Q000188:drug therapy; D010641:Phenotype; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology; D011134:Polysaccharides / Q000737:chemistry; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D053038:Quorum Sensing / Q000187:drug effects*; D014031:Tobramycin / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D014329:Tropical Climate; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: C000607329:3-hydroxyolean-12-en-28-al 3-p-coumarate; D054742:Acyl-Butyrolactones; D000447:Aldehydes; D000900:Anti-Bacterial Agents; D003373:Coumaric Acids; D010936:Plant Extracts; D011134:Polysaccharides; D014315:Triterpenes; D037521:Virulence Factors; D009828:Oleanolic Acid; D014031:Tobramycin