# Antibacterial potential, DNA binding and molecular docking investigations of newly green synthesized zinc oxide/chitosan/vancomycin nanocomposite using Bacillus licheniformis ATCC 4527 against some drug-resistant bacteria

## TL;DR

A new green-synthesized nanocomposite shows strong antibacterial activity against drug-resistant bacteria and is safe for use.

## Contribution

A novel green-synthesized zinc oxide/chitosan/vancomycin nanocomposite with enhanced antibacterial activity and safety is introduced.

## Key findings

- The ZnO/CS/VA nanocomposite showed superior antibacterial activity against MDR strains compared to ZnO or vancomycin alone.
- Molecular docking revealed strong binding with scores from -0.7 to -10.85 kcal/mol.
- The nanocomposite exhibited low cytotoxicity with CC50 values of 146.62 and 162.86 μg/mL for ZnO NPs and ZnO/CS/VA, respectively.

## Abstract

The increasing crisis of multidrug-resistant (MDR) bacteria requires the creation of new, highly effective, and safe antibacterial agents. This study introduces a simple and cost-effective green synthesis method for a novel zinc oxide/chitosan/vancomycin (ZnO/CS/VA) nanocomposite to improve antibacterial activity against priority MDR strains. Zinc oxide nanoparticles (ZnO NPs) were biosynthesized using Bacillus licheniformis ATCC 4527 and then combined with vancomycin (VA) and chitosan (CS) in an environmentally friendly process. Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), ultraviolet-visible spectroscopy (UV-Vis), and zeta potential studies were conducted to validate and characterize the production of ZnO/CS/VA. The antibacterial activity of the nanoparticles was tested against several multidrug-resistant (MDR) strains, including Bacillus cereus HES3, methicillin-resistant S. aureus (MRSA), Escherichia coli D8, Pseudomonas aeruginosa, and Klebsiella pneumoniae H4. Further assessment included molecular docking interactions with E. coli (PDB: 3T88) and MRSA (PDB: 4DKI) targets, CT-DNA binding, and cytotoxicity testing on the Vero cell line. Characterization confirmed the successful formation of the nanocomposite, revealing ZnO nanoparticles ranging from 33.24 to 69.11 nm and high stability (zeta potential: -17.78 mV). The ZnO/CS/VA nanocomposite exhibited superior dose-dependent antibacterial activity compared to ZnO nanoparticles or VA alone against all tested MDR strains, including MRSA and E. coli D8. Molecular docking demonstrated strong binding, with scores ranging from -0.7 to -10.85 kcal/mol. The nanocomposite exhibited a hypochromism when interacting with CT-DNA, suggesting intercalation. Importantly, the CC50 values of ZnO NPs and ZnO/CS/VA against Vero cells were 146.62±1.03 and 162.86±1.07 μg/mL, respectively, indicating their high level of safety.

The green-synthesized ZnO/CS/VA nanocomposite is a promising alternative candidate for treating various MDR bacterial infections. It offers utility in biomedical and pharmaceutical applications due to its high efficacy and low cytotoxicity.

The online version contains supplementary material available at 10.1186/s12934-026-02928-9.