Synergistic effect of green synthesized zinc oxide nanoparticles coupled with various antibiotics against emerging multidrug resistant bacteria: characterization and therapeutic potentials evaluation

Abstract

Background

Antibiotic resistance is a worldwide health crisis that threatens public health systems and medical regimens, underscoring the urgent need for new antibacterial drugs. Hence, this study aimed to investigate the antibacterial efficacy of biosynthesized zinc oxide nanoparticles (ZnONPs) utilizing rosemary leaves (RL) and pomegranate peels aqueous extracts (PPAEs) against pathogenic multidrug-resistant (MDR) bacteria either alone or with antibiotics along with their antioxidant and cytotoxic potential.

Results

Antibiotic susceptibility tests revealed higher rates of resistance among Staphylococcus aureus (93.7%) than among the Gram-negative pathogens, K. pneumoniae (91.7%), E. coli (89.6%) and P. aeruginosa (75%). Importantly, two K. pneumoniae strains and two S. aureus strains, were found to be resistant to all the antibiotics tested, including Imipenem (Carbapenems) and Vancomycin & Teicoplanin (Glycopeptides), which are considered the last line of defense against MDR microbes. The prepared ZnONPs utilizing RL and PPAEs were characterized via UV–visible spectroscopy, which revealed characteristic peaks at 300 and 310 nm, respectively. High–resolution transmission electron microscopy (HRTEM), revealed spherical and hexagonal shapes, respectively, and zeta potential analysis, revealed that the surface charges of the ZnONPs were -13.3 and -37.0 mV, respectively, and X-ray diffraction (XRD) was used to verify the crystal structure and Fourier transform infrared (FTIR) spectra of the ZnONPs, confirming the identity of the distinct functional groups in the ZnONPs. The formed ZnONPs utilizing RL and PPAEs exhibited significant antibacterial efficiency, with inhibitory zones of 13.5 ± 0.3 – 25 ± 0.2 and 13 ± 0.1 – 23 ± 0.2 mm, respectively, against Gram-negative bacteria and 15 ± 0.1 – 21.3 ± 0.3 and 13 ± 0.1 – 15 ± 0.1 mm, respectively, against S. aureus. Moreover, ZnONPs displayed significant synergistic effects with Ampicillin/Sulbactam, Cefotaxime and Norfloxacin against the tested bacteria, including those that were resistant to all the antibiotics tested. The ZnONPs produced via RLAE exhibited greater antioxidant activity than those produced utilizing PPAE. Interestingly, the ZnONPs bioformed via RL and PPAEs had CC50 values of 497 ± 0.8 and 85.69 ± 0.3 µg/ml, respectively, in human lung fibroblast (MRC-5) cells, confirming their safety in normal cells and IC50 values of 212 ± 0.5 and 27.93 ± 0.2 µg/ml, respectively, in hepatocellular carcinoma (HepG-2) cells, revealing their promising anticancer potential.

Conclusions

Green ZnONPs synthesized utilizing RL and PPAEs were found to be safe and nontoxic and may pave the way for future combination therapy against MDR bacteria because of their potential synergistic impact with antibiotics.

Clinical trial number

Not applicable.