Assessment of MgO, ZnO, chitosan hydroxyapatite and silver hydroxyapatite nanoparticles against carbapenem-resistant Gram-negative Egyptian clinical isolates: a combined in-silico and in-vitro study.

BACKGROUND: Currently, antimicrobial resistance (AMR) is one of the major global threats to public health; therefore, treating infectious diseases becamemore challenging. In Egypt, the prevalence of carbapenem-resistant Gram-negative bacteria has notably increased, presenting substantial challenges to infection control and therapeutic strategies. New treatment approaches including nanoparticles have been discovered to combat antibiotic resistance. OBJECTIVE: We evaluated the potential of nanoparticles as next-generation antimicrobials through a dual approach combining computational modeling and antimicrobial testing of different nanoparticles (NPs); magnesium oxide (MgO NPs), zinc oxide (ZnO NPs), chitosan hydroxyapatite (ChHap NPs) and silver hydroxyapatite (AgHap NPs) against standard strains and clinical bacterial isolates. RESULTS: The Minimum inhibitory concentration(MIC) showed that AgHap NPs exhibited MIC value of 1.875 mg. mL-1 against all the tested bacterial isolates, while MgO NPs exhibited MIC values of 1.5, 1.5, 0.75 and 0.375 mg/mL against E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, respectively. The cytotoxicity profiles of the nanoparticles were assessed using the human hepatocellular carcinoma cell line (HepG2), demonstrating approximately 40–85% cell viability at concentrations near MIC values of the AgHap NPs and MgO NPs. A molecular docking study revealed that all tested NPs have affinity to gyrase enzyme inE.coli,transmission electron microscope images (TEM) also revealed a significant disruption of the bacterial cell wall integrity, indicating a potential mechanism of action. CONCLUSION: Collectively, MgO NPs and AgHap NPs are promising alternative therapeutic agents for the treatment of resistant Gram-negative clinical infections.