Quercetin: a promising virulence inhibitor of Pseudomonas aeruginosa LasB in vitro
Abstract
Abstract With the inappropriate use of antibiotics, antibiotic resistance has emerged as a major dilemma for patients infected with Pseudomonas aeruginosa . Elastase B (LasB), a crucial extracellular virulence factor secreted by P. aeruginosa , has been identified as a key target for antivirulence therapy. Quercetin, a natural flavonoid, exhibits promising potential as an antivirulence agent. We aim to evaluate the impact of quercetin on P. aeruginosa LasB and elucidate the underlying mechanism. Molecular docking and molecular dynamics simulation revealed a rather favorable intermolecular interaction between quercetin and LasB. At the sub-MICs of ≤256 μg/ml, quercetin was found to effectively inhibit the production and activity of LasB elastase, as well as downregulate the transcription level of the lasB gene in both PAO1 and clinical strains of P. aeruginosa . Through correlation analysis, significant positive correlations were shown between the virulence gene lasB and the QS system regulatory genes lasI , lasR , rhlI , and rhlR in clinical strains of P. aeruginosa . Then, we found the lasB gene expression and LasB activity were significantly deficient in PAO1 ΔlasI and ΔlasIΔrhlI mutants. In addition, quercetin significantly downregulated the expression levels of regulated genes lasI , lasR , rhlI, rhlR , pqsA , and pqsR as well as effectively attenuated the synthesis of signaling molecules 3-oxo-C12-HSL and C4-HSL in the QS system of PAO1. Quercetin was also able to…
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