Biogenic Selenium Nanoparticles as Efflux Pump Inhibitors in Multidrug-Resistant Pseudomonas aeruginosa: An In Vitro and In Silico Approach
Abstract
Background: Multidrug-resistant (MDR) Pseudomonas aeruginosa is a serious global health concern due to the overexpression of the efflux pump system MexAB-OprM. An innovative approach to the synthesis of nanoparticles using biogenic selenium (SeNPs) has shown promising antimicrobial properties and potential for efflux pump inhibitory activity. Objective: This study focused on the synthesis of selenium nanoparticles using leaf extract from Ziziphus spina-christi and an integrated in vitro and in silico study of their activity as efflux pump inhibitors against MDR P. aeruginosa. Methods: Clinical MDR P. aeruginosa isolates were identified using 16S rRNA gene sequencing. Green-synthesized SeNPs were characterized using UV-Vis, FTIR, and SEM. MICs were determined, and antibiotic-synergy associated FIC index (FICI) calcukations and checkerboard assauys were performed. MexAB-OprM efflux pump gene expression was quantified using RT-qPCR. Molecular docking was conducted for predicting interactions of SeNPs with MexA, MexB, and OprM proteins. Results: Biogenic synthesis SeNPs showed absorption peaks between 265 and 280 nm and had a spherical shape and a dia of 20-45 nm. SeNPs exhibited a strong antibacterial effect against multi-drug resistant (MDR) P. aeruginosa and showed a synergistic effect with imipenem (FICI: 0.25-0.375) (MIC: 16-32 (µg/mL). RT-qPCR results showed a significant downregulation of mexA, mexB, and oprM genes (2.5-4.8 fold; p<0.001). In silico molecular docking…
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