In silico study of anti-quorum sensing activity of silver, zinc oxide, and copper oxide nanoparticles against Pseudomonas aeruginosa

Abstract

Abstract In recent years, Pseudomonas aeruginosa emerged as a significant pathogenic microorganism in the majority of hospital-acquired infections due to the elevated levels of resistance to antibacterial agents by virtue of its highly organized quorum sensing (QS). P. aeruginosa has three hierarchical major QS systems (LasI/R, RhlI/R, and PqsA/R) that are involved in the secretion of virulence factors, biofilm formation, and antimicrobial resistance. Thus, targeting the QS mechanism may be a good strategy to combat infection caused by P. aeruginosa . In the present study, in silico analysis by molecular docking simulation of anti-quorum sensing activities of silver, zinc oxide and copper oxide against P. aeruginosa strain have been evaluated. Molecular docking showed that metal/metal oxide interaction with Acyl-Homoserine-Lactone synthases (LasI, RhlI, PqsA) can prevent precursor molecule binding and therefore inhibit the synthesis of functional signaling molecules. In addition, the binding of these nanoparticles to regulatory proteins (LasR, RhlR, PqsR) decreases the expression of QS-controlled genes by competing with functional signaling molecules for interaction with regulatory proteins. Thus, our results revealed that ZnO possesses good binding properties towards the selected targets. Particularly, the PqsA-ZnO complex shows more stable active binding sites and better binding affinity (-3.83 kcal/mol) with an inhibitory constant (Ki) of 1.65 mM. The binding mode of ZnO nanoparticles (NPs) has been found to be more potent compared to Ag and CuO NPs and related to the virulence factors of Gram-negative bacterial pathogens. This suggests that ZnO NPs could potentially be developed as effective inhibitors of QS systems and biofilms.