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.