Journal Article

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

Huet, Joelle, Duez, Pierre, El Jaziri, Mondher, Rasamiravaka, Tsiry, Rasamindrakotroka, Andry, Vandeputte, Olivier M., Kiendrebeogo, Martin, Andriantsimahavandy, Abel, Stévigny, Caroline, Pottier, Laurent, Rabemanantsoa, Christian

2015

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acids / Acyl-Butyrolactones - metabolism / Aldehydes - pharmacology / Animals / Anti-Bacterial Agents - pharmacology / Antibacterial agents / Antibiotics / Antifungal agents / Antimicrobial agents / Bacteria / Bacterial infections / Bactericidal activity / Bark / Bioactive compounds / Biofilms / Biofilms - drug effects / Biofilms - growth & development / Caenorhabditis elegans - drug effects / Chromatography / Coumaric Acids - chemistry / Coumaric Acids - isolation & purification / Coumaric Acids - pharmacology / Coumaric Acids - therapeutic use / Dalbergia / Dalbergia - chemistry / Draba trichocarpa / Drug resistance / Drug Synergism / Elastase / Endangered & extinct species / Esters / Extracellular matrix / Gene Expression Regulation, Bacterial - drug effects / Genes, Bacterial / Infections / Inhibition / Lactones / Legumes / Movement - drug effects / Nutrition / Oleanolic Acid - analogs & derivatives / Oleanolic Acid - chemistry / Oleanolic Acid - isolation & purification / Oleanolic Acid - pharmacology / Oleanolic Acid - therapeutic use / Paralysis / Paralysis - drug therapy / Pathogens / Phenotype / Plant Bark - chemistry / Plant Extracts - pharmacology / Polysaccharides / Polysaccharides - chemistry / Pseudomonas / Pseudomonas aeruginosa / Pseudomonas aeruginosa - drug effects / Pseudomonas aeruginosa - genetics / Pseudomonas aeruginosa - pathogenicity / Pseudomonas aeruginosa - physiology / Pyocyanin / Quorum Sensing - drug effects / Regulation / Rhamnolipids / Saccharides / Swarming / Tobramycin / Tobramycin - pharmacology / Triterpenes - chemistry / Triterpenes - isolation & purification / Triterpenes - pharmacology / Triterpenes - therapeutic use / Tropical Climate / Twitching / Virulence / Virulence factors / Virulence Factors - metabolism