Effects of natural compounds and commercial antibiotics on Pseudomonas aeruginosa quorum sensing

Pseudomonas aeruginosa is a Gram-negative bacterium designated by the WHO as a critical priority microorganism due to its virulence, controlled by a quorum sensing (QS) system. QS is regulated} through specific subsystems: LasI/LasR, RhlI/RhlR, and PQS/MvfR. Several natural compounds can inhibit these QS mechanisms. In this study, we determined the effect of curcumin, reserpine, and their mixtures with two commercial antibiotics (gentamicin and azithromycin) on P. aeruginosa QS mechanisms: mvfR gene expression and the production of pyocyanin and rhamnolipids. Antibiotic and natural compounds’ minimal inhibitory concentrations (MICs) were determined via microdilution assays. Gentamicin, azithromycin, curcumin, reserpine, and their mixtures exerted variable effects on mvfR gene expression, as assessed via semi-quantitative RT-PCR assays. Curcumin, reserpine, and gentamicin inhibited mvfR gene expression better than azithromycin, and the mixtures curcumin-gentamicin and reserpine-gentamicin outperformed gentamicin alone in inhibiting mvfR gene expression and decreasing pyocyanin and rhamnolipids production, revealing the synergistic effect of these mixture components. The mixtures of curcumin and gentamicin and reserpine and gentamicin may become alternatives to complement or enhance conventional methods currently used to treat P. aeruginosa infections.