This study investigated the green synthesis of Zn-MnO nanocomposites via the fungus Penicillium rubens. Herein, the synthesized Zn-MnO nanocomposites were confirmed by UV-spectrophotometry with a top peak (370 nm). Transmission electron microscopy confirmed irregular particles with a spherical-like shape ranging from 25.13 to 36.21 nm. Numerous functional groups were detected on the surface of Zn-MnO nanocomposite via Fourier-transform infrared spectroscopy. X-Ray diffraction assay appeared that the synthesized Zn-MnO nanocomposites contained two different components, MnO (JCPDS 81-2261) and ZnO (JCPDS 36-1451), while energy dispersive X-ray spectra confirmed the occurrence of manganese, zinc, oxygen, and carbon in Zn-MnO nanocomposites. Zn-MnO nanocomposites demonstrated excellent suppress effect versus the growth of various bacteria namely Staphylococcus aureus, Methicillin-resistant S. aureus (MRSA), Salmonella typhi, and Klebsiella pneumoniae via agar well diffusion assays with inhibition areas of 36 ± 0.1, 25 ± 0.1, 27 ± 0.2, and 23 ± 0.2 mm, correspondingly. Alterations in the ultrastructure of the treated K. pneumoniae by Zn-MnO nanocomposite were recorded. Both the values of minimum inhibitory concentration (MIC) and minimum bactericidal concentration of Zn-MnO nanocomposite extended from 15.62 to 125 µg/mL employing the examined bacteria. The antibiofilm activity of Zn-MnO nanocomposites was 82.07, 75.43, 43.65, and 41.35% at 25% MIC, and 96.54, 93.0, 94.53, and 91.11% at 75% MIC against S. aureus, MRSA, K. pneumoniae, and S. typhi, respectively. At 25 to 75% MIC, Zn-MnO nanocomposites exhibited antihemolytic activity with the maximum activity of 96.3% at 75% MIC in the presence of MRSA. Extensive molecular docking studies were performed to identify the optimal location for manganese oxide and zinc oxide nanoclusters binding to MRSA. MnO-NPs and ZnO-NPs demonstrated inhibitory activity against the crystal structure of putative minohydrolase (PDB ID: 4EWT), methicillin acyl-penicillin binding protein 2a structure (PDB ID: 1MWU) and K2U bound crystal structure of class II peptide deformylase from MRSA (PDB ID: 6JFQ). The minimum binding energy was utilized to estimate the receptor’s binding site with NPs, providing additional understanding of the ways of action. Anti-inflammatory activity of Zn-MnO nanocomposites via cyclooxygenase-1 and cyclooxygenase-2 enzymes inhibition was documented with IC50 doses of 20.81 ± 0.68 µg/mL and 35.87 ± 1.35 µg/mL, respectively. Based on these outcomes, it was concluded that Zn-MnO nanocomposites could be useful agents for the management of multidrug resistant bacterial pathogens and inflammation.
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