In vitro and in vivo efficacy of zinc oxide green nanoparticles against multidrug-resistant Salmonella Typhi.

Antibiotic resistance is an increasing threat, requiring novel therapeutic solutions. Metal nanoparticles e.g., zinc oxide nanoparticles (ZnO NPs) exhibited the potential against many bacterial pathogens. Strains of Salmonella enterica serovar Typhi resistant to ceftriaxone were reported first from Pakistan in 2016. Since then, S. Typhi is a pathogen of concern globally owing to its rapidly emerging resistance potential against many last resort antibiotics. In the present study, in vitro and in vivo antimicrobial activity of ZnO NPs against multidrug resistant (MDR) and extensively drug resistant (XDR) Salmonella Typhi strains from Pakistan was evaluated. Zinc oxide green nanoparticles (ZnO GNPs), synthesized from Aloe vera, were characterized by SEM, XRD, UV-vis and Raman spectroscopy. In vitro antibacterial activity of two different concentrations of ZnO GNPs (7 and 15%) was checked using agar well diffusion method. Further, broth microdilution and time kill assays were performed using the ZnO GNPs. In vivo assays were conducted in BALB/c mice sepsis models. In all the three methods, agar well diffusion assay broth microdilution and time kill assay, different zinc oxide dihydrate precursor concentrations had shown the antibacterial activity. The minimum inhibitory concentration (MIC) of ZnO GNPs nanoparticles against MDR and XDR S. Typhi strains was found as 16 to 64 µg/ml. In vivo experiment has shown a significant decrease in CFU/ml in the mice treated with ZnO GNPs as compared to the control group. Our findings have revealed that ZnO GNPs have significant antibacterial activity against MDR and XDR S. Typhi, both in vitro and in vivo.