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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.

plos one

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