Molecular biology insights into levofloxacin-loaded ZnO nanoparticles: a potent strategy against MDR <i>Acinetobacter baumannii</i>

Antibiotic resistance is a major global health threat, reducing the effectiveness of standard treatments and increasing mortality rates. This study explores the potential of zinc oxide nanoparticles (ZnO-NPs), synthesized using <i>Streptococcus mitis</i> biomass, to combat levofloxacin-resistant <i>Acinetobacter baumannii</i>. ZnO-NPs were conjugated with levofloxacin (LFX), and their antibacterial activity was evaluated both alone and in combination with antibiotics. Characterization using FTIR, XRD, DLS, FE-SEM-EDX, and UV-Vis confirmed quasi-spherical ZnO-NPs with an average size of 17.62 nm. The antifungal efficacy of the ZnO-NPs nanocomposite was also tested against <i>Candida albicans</i>, <i>Candida glabrata</i>, and <i>Candida krusei</i> at concentrations from 1000 to 62.5 μg mL^-1. Mechanistic studies revealed that ZnO-NPs induce membrane lipid peroxidation, elevate malondialdehyde and reactive oxygen species (ROS) levels, and cause DNA damage, protein denaturation, and membrane leakage in bacterial cells. These results indicate that biosynthesized ZnO-NPs, especially when conjugated with antibiotics, exhibit significant antimicrobial activity against multidrug-resistant pathogens, highlighting their potential as alternative therapeutic agents in addressing antibiotic resistance.