Effect of Sub-Minimum Inhibitory Concentrations of Tyrosol and EDTA on Quorum Sensing and Virulence of Pseudomonas aeruginosa

Introduction: Pseudomonas aeruginosa is considered a dangerous pathogen, as it causes many human diseases, besides that it is resistant to almost all types of antibacterial agents. So, new strategies to overcome P. aeruginosa infection have evolved to attenuate its virulence factors and inhibit its quorum-sensing (QS) activity. Purpose: This study investigated the effect of tyrosol and EDTA as anti-quorum-sensing and antivirulence agents against P. aeruginosa PAO1. Methods: Anti-quorum activity of sub-minimum inhibitory concentrations (sub-M1Cs) of tyrosol and EDTA was tested using Chromobacterium violaceum (CV 12,472) biosensor bioassay. Miller assay was used to assess the inhibition of QS signal molecules by beta-galactosidase activity determination. Also, their effects on the production of protease, lipase, lecithinase, and motility were tested. The inhibitory effects of these molecules on QS regulatory genes and exotoxins genes expression were evaluated by real-time PCR. Results: Tyrosol and EDTA at sub-M1Cs inhibited the production of violacein pigment. Both compounds inhibited QS molecules production and their associated virulence factors (protease, lipase, lecithinase, and motility) (P <= 0.05). Besides, the expression levels of QS regulatory genes (lasI, lasR, rhII, rhIR, pqsA, and pqsR) and exotoxins genes (exoS and exoY) were significantly reduced (P <= 0.05). Conclusion: Both tyrosol and EDTA can be used to fight P. aeruginosa infection as antiquorum-sensing and anti-virulence agents at their sub-MICs.