Browsing by Author "Hussan, Raeesa Hoosen"

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    Investigation of the antimycobacterial activity of fungal endophytes and their magnetic dendrimer stabilized nanoparticles against mycobacteria
    (Stellenbosch : Stellenbosch University, 2024-03) Hussan, Raeesa Hoosen; Mavumengwana, Vuyo; Malgas-Enus, Rehana; Loxton, Andre Gareth; Allie, Nasiema; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Molecular Biology and Human Genetics.
    ENGLISH ABSTRACT: Tuberculosis (TB), is a disease caused by a single infectious agent Mtb, remains a global health threat that claimed the lives of 1.4 million people worldwide between 2020- 2021. Despite current anti tuberculosis treatment, TB remains one of the leading causes of infection highlighting the imminent need for drug discovery of alternative and novel treatments with distinct modes of action against Mycobacteria. In this context, the present study investigated the antimycobacterial activities of fungal endophyte metabolites functionalized on magnetic dendrimer stabilized nanoparticles (DSNPs) against mycobacterial models. To achieve the aim, fungal endophytes were isolated from four Fynbos families (Asteraceae, Lamiaceae, Ericaceae, and Droseraceae), sequenced and identified by phylogeny. Methanolic crude extracts obtained from cultivated fungi were tested for antimycobacterial activity against Mycobacterium tuberculosis H37Rv (Mtb H37Rv) and Mycobacterium smegmatis mc2155 (Msmeg mc2155). Metabolites within the bioactive fungal extracts were identified by untargeted liquid chromatography-mass spectrometry (LC-QTOF-MS/MS). The infection of THP-1 macrophage cells with Msmeg mc2155 was performed to determine the intracellular antimycobacterial activity of fungal crude extracts. The DSNPs were synthesized from modified magnetic iron oxide nanoparticles (MIONs) and G3-dendrimer micelles. Microscopic and spectral techniques (SEM, FTIR, UV-Vis, and ICP-AES) were used to characterize nanoparticles, followed by antimycobacterial activity assays. Twenty unique fungal isolates were identified with Penicillium being the abundant genera. Penicillium thomii, Diaporthe leucospermi, Penicillium rubens, Cadophora sp. and Penicillium sp. possess antimycobacterial activity. Cadophora sp. demonstrated the most significant inhibition of Msmeg mc2155 and the bioactivity was enhanced in the host-directed approach against intracellular Msmeg mc2155. The metabolites N-benzyl-1-tetradecanamine, N-benzyl-1-hexadecanamine, asperthecin, meleagrin, roquerfortine F, chlamydocin and neoxaline, (-)5-methylmellein, and 9-octadecenamide were identified with the latter two possessing antimycobacterial activity. The nanoparticles (G3- dendrimer micelles, MIONs and DSNPs) were successfully synthesized. G3-dendrimer micelles and DNSPs inhibited Msmeg mc2155 and the former Mtb H37Rv. MIONs possessed enhanced bioactivities against intracellular Msmeg mc2155. Functionalization of DSNPs with bioactive metabolites (nano metabolites) demonstrated no antimycobacterial activity against Msmeg mc2155 directly but antimycobacterial activity was observed intracellularly. Enhanced activity of nano-metabolites was observed directly against Mtb H37RV. Fungal extracts, nanoparticles and functionalized nanoparticles have distinct mechanisms of antimycobacterial activities against the strains of mycobacteria (Msmeg mc2155 and Mtb H37Rv). This study highlighted that the properties of nanoparticles greatly influence their antimycobacterial activities i.e., the ferrous content of a naked nanoparticle opposed to a modified nanoparticle. Functionalization of a nanoparticle contributes to its modification which has an impact on the antimycobacterial activity. Hence, this necessitates further investigations about nanoparticles, their properties and modifications against mycobacterial models. In addition, the nanoparticles have the potential to be modified to accommodate or scaffold existing anti-Tb drugs and to potentiate antimycobacterial effects through pathogen- and host directed approaches.