Metal and Metal Oxide Nanoparticles: Computational Analysis of Their Interactions and Antibacterial Activities Against Pseudomonas aeruginosa

The effectiveness of antibiotics against Pseudomonas aeruginosa (P. aeruginosa) infections is limited by inherent antimicrobial resistance, prompting researchers to seek advanced and cost-effective antibacterial agents. This opportunistic bacterium exhibits drug resistance and regulates its pathogenicity through quorum sensing (QS) mechanisms, suggesting that disrupting these systems could be a promising approach to treating P. aeruginosa infections. In this study, we investigated the antibacterial properties of silver nanoparticles (AgNPs), zinc oxide nanoparticles (ZnONPs), and copper oxide nanoparticles (CuONPs) in conjunction with QS systems, focusing on the LasI/R, RhlI/R, and PqsA/PqsR pathways. A computational approach was utilized to examine the interaction patterns between these nanoparticles and QS signaling proteins in P. aeruginosa through multiple bioinformatics techniques. The interaction of metals and metal oxides with acyl-homoserine-lactone synthases (LasI, RhlI, PqsA) can impede the binding of precursor molecules, thereby inhibiting the synthesis of functional signaling molecules. Moreover, the binding of nanoparticles to regulatory proteins (LasR, RhlR, PqsR) competes with functional signaling molecules, resulting in a reduced expression of QS-controlled genes. Among the nanoparticles studied, ZnONPs exhibited the highest affinity toward the selected targets. In particular, the PqsA-ZnONPs complex showed stable active binding sites and a high binding affinity (− 3.83 kcal/mol), indicating strong interaction with the active pocket of the pathogen P. aeruginosa (PqsA: 5OE3). ZnO nanoparticles demonstrated significant potential as antimicrobial agents against P. aeruginosa by disrupting its QS systems. This approach presents a promising direction for developing therapeutic strategies to combat antibiotic-resistant bacteria, including P. aeruginosa. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.