Microbial resistance is a major public health concern, leading to treatment failure, prolonged hospitalization, and increased mortality. Developing new, cost-effective antimicrobial agents is critical. This study presents a simple, economical, and eco-friendly (green) synthesis of zinc oxide nanoparticles (ZnO NPs) using bioactive metabolites from the mushroom Lepista sordida EGDA2 as a bio-nano-factory. The resulting ZnO NPs were characterized by ultraviolet–visible spectroscopy (UV–Vis), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and zeta potential analysis, while the bioactive capping agents were profiled using GC–MS. UV–Vis analysis confirmed ZnO NP formation with a characteristic absorption peak at 301 nm, and XRD and TEM revealed crystalline wurtzite-structure nanoparticles (NPs) with an average size of approximately 33 nm (18–46 nm). FTIR and GC–MS indicated the presence of stabilizing bioactive compounds, notably fatty acids (e.g., palmitic acid, oleic acid) and polyphenols, and the NPs exhibited good colloidal stability, with a zeta potential of − 21.83 ± 4.25 mV. The biosynthesized ZnO NPs showed potent, dose-dependent antimicrobial and antibiofilm activities against a panel of drug-resistant bacteria (e.g., MRSA and Pseudomonas aeruginosa) and pathogenic fungi (e.g., Candida albicans and Aspergillus niger), with minimum microbicidal concentration (MMC) values correlating with minimum inhibitory concentration (MIC) values and up to 70% inhibition of biofilm formation in MRSA and P. aeruginosa at 150 µg/mL, consistent with the reported antibiofilm potential of green-synthesized ZnO NPs. The NPs also exhibited strong antioxidant activity in the DPPH assay (78.1% inhibition) and interacted with calf thymus DNA (CT-DNA) via an intercalative binding mode, in line with previous reports on ZnO NP–DNA interactions. Cytotoxicity assessment using the MTT assay on Vero cells yielded a high CC50 value of 208.17 ± 1.94 µg/mL, indicating that the biogenic ZnO NPs are biocompatible at their effective antimicrobial and antibiofilm concentrations (≤ 150 µg/mL), which agrees with the generally favorable biocompatibility profile reported for green-synthesized ZnO NPs on Vero cells. This work presents a promising, safe, and effective alternative treatment utilizing green synthesized ZnO NPs capped with bioactive compounds from L. sordida EGDA2. The resulting NPs demonstrate synergistic antioxidant, antimicrobial, and significant antibiofilm activities, offering promising applications in industrial, pharmaceutical, and environmental applications.
El-fallal et al. (Thu,) studied this question.