Bioconjugated zinc oxide–quercetin nanocomposite enhances the selectivity and anti-biofilm activity of ZnO nanoparticles against Staphylococcus species

Quercetin (Q), a plant-derived flavonoid, has antibacterial properties against a wide range of bacterial types, and preferentially targets gram-positive bacteria. However, because of its lower activity than that of current antibiotics, Q has only been used as an antimicrobial adjuvant, particularly against antimicrobial-resistant strains, where it works synergistically with other agents to increase their antimicrobial activity and selectivity. Zinc oxide (ZnO) nanomaterials, which are among the most extensively researched and powerful antibacterial compounds, have limitations in terms of off-target effects and cytotoxicity at high concentrations and this necessitates the use of biocompatible chemicals for their modification. In this study, we bio-conjugated ZnO with Q using cell-free supernatant of Staphylococcus ATCC 25923. UV–visible spectroscopy, X-ray diffraction analysis, Fourier-transform infrared spectroscopy, dynamic light scattering, and transmission electron microscopy confirmed the formation of ZnO nanoparticles (NPs) with Q nanocomposite (ZnO@Q NC). The in vitro antibacterial activity of ZnO@Q NC against gram-negative and gram-positive bacterial species was evaluated as the minimum inhibitory concentration. The results demonstrated that ZnO@Q NC exhibited a 4–32-fold higher preferential activity toward Staphylococcus species than Q and ZnO NPs. Additional mechanistic studies revealed that ZnO@Q NC disrupted bacterial membranes and prevented biofilm formation. The biocompatibility of ZnO@Q NC with WI-38 cells was assessed, and the synergistic use of ZnO@Q NC with antibiotics was suggested to reduce its cytotoxicity. Overall, the results demonstrated that conjugating ZnO NPs with Q can significantly boost their bactericidal efficacy and selective pressure against Staphylococcus species.

Graphical abstract