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Mycobacterium tuberculosis metallomics
Thesis (PhD)--Stellenbosch University, 2026.
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| Format: | Thesis |
| Language: | English |
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Stellenbosch : Stellenbosch University
2026
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| _version_ | 1867614037863301120 |
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| access_status_str | Open Access |
| author | Badejo, Motunrayo Victoria |
| author2 | Mavumengwana, Vuyo |
| author_browse | Badejo, Motunrayo Victoria Mavumengwana, Vuyo |
| author_facet | Mavumengwana, Vuyo Badejo, Motunrayo Victoria |
| author_sort | Badejo, Motunrayo Victoria |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)--Stellenbosch University, 2026. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/135584 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:45:40.774Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2026 |
| publishDateRange | 2026 |
| publishDateSort | 2026 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/135584 Mycobacterium tuberculosis metallomics Badejo, Motunrayo Victoria Mavumengwana, Vuyo Baatjies, Lucinda Tapfuma, Kudzanai Kinnear, Craig Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Division of Molecular Biology & Human Genetics. Thesis (PhD)--Stellenbosch University, 2026. Badejo, M. V. 2026. Mycobacterium tuberculosis metallomics. Unpublished doctoral dissertation. Stellenbosch: Stellenbosch University [online]. Available: https://scholar.sun.ac.za/items/c1b14f32-ac66-4b5d-be59-4979290dac2c Tuberculosis (TB) remains a major global health challenge, compounded by the rise of drug-resistant Mycobacterium tuberculosis (Mtb) strains, which necessitate the development of novel therapies or improvement of existing ones. Nanotechnology has gained prominence in the biomedical field, yet its application in TB treatment remains underexplored. This study investigated the role of metal-based nanoparticles as potential antimycobacterial agents. Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesised via co-precipitation of ferric chloride and ferric sulphate. The SPIONs were subsequently surface modified with secondary metals (Ag, Au, Cu, Ni) to generate bimetallic systems (Ag@SPIONs, Au@SPIONs, Cu@SPIONs, Ni@SPIONs) or trimetallic systems (Ag-Cu@SPIONs and Ag-NI@SPIONs). Structural characterisation was performed using scanning transmission electron microscopy (STEM), energy-dispersive X-ray spectroscopy (EDX), UV-Visible spectroscopy, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), superconducting quantum interference device (SQUID) magnetometry, zeta potential analysis, and inductively coupled plasma mass spectrometry (ICP-MS). The antimycobacterial efficacy of SPIONs and metal-coated SPIONs was evaluated against Mycobacterium smegmatis (Msmeg) and Mtb using time–kill assays. Nanoparticle–bacterium interactions were further characterised through microscopy techniques and ICP–MS. To elucidate molecular responses, transcriptomic analyses were performed to assess the impact of nanoparticle exposure on bacterial physiology. Ex vivo toxicity study was conducted on murine (RAW 264.7) cell line to assess the safety of the nanoparticle systems. Furthermore, the capacity of SPIONs and their metal-coated derivatives to potentiate the activity of repurposed anti-TB compounds was also investigated through time–kill assays. The SPIONs and their metal-coated derivatives exhibited average sizes less than 20 nm, with elemental mapping confirming the incorporation of secondary metals. The surface charge and optical properties were altered due to surface modification, including a UV-Vis absorption shift from 237 nm (SPIONs) to 247 nm (metal-coated SPIONs). FTIR spectra revealed additional functional groups in metal-coated SPIONs, while XRD confirmed magnetite crystalline phases across all formulations. Magnetometry analysis demonstrated superparamagnetic behaviour. ICP-MS analysis revealed iron (Fe) as the dominant component of the metal-coated systems, as expected. Antimycobacterial activity of bimetallic and trimetallic SPIONs against Msmeg followed the order: Ag-Cu@SPIONs > Ag-Ni@SPIONs > Ag@SPIONs > Cu@SPIONs > Ni@SPIONs, with MIC values of 1.95 μg/mL, 3.9 μg/mL, 3.9 μg/mL, 62.5 μg/mL, and >62.5 μg/mL, respectively. Au@SPIONs and naked SPIONs showed no inhibitory activity. Microscopy study revealed distinct phenotypic alterations in Msmeg cells exposed to metallic treatments: Ag@SPIONs shortened cell length, Cu@SPIONs induced cell clumping, and Ag-Cu@SPIONs caused membrane rupture. Transcriptomic analysis revealed that Ag@SPIONs and Ag-Cu@SPIONs disrupted sulphur metabolism and oxidoreductase pathways in Msmeg, while Cu@SPIONs interfered with amino acid and fatty acid metabolism. Against Mtb, Ag@SPIONs, Cu@SPIONs, and Ag-Cu@SPIONs displayed antimycobacterial activity with MIC values of 62.5 μg/mL, 62.5 μg/mL, and 31.25 μg/mL, respectively. Exposure of Mtb to these nanoparticles caused phenotypic changes characterised by the induction of filamentation and loss of extracellular vesicles. Notably, cytotoxicity assessments demonstrated that both unmodified SPIONs and their metal-coated derivatives were well tolerated by RAW 264.7 macrophages. Furthermore, drug-functionalised SPIONs exhibited enhanced antimycobacterial efficacy compared to free drugs or unmodified SPIONs. Sulfadiazine-functionalised formulations (S_Ag@SPIONs, S_Cu@SPIONs, and S_Ag-Cu@SPIONs) achieved MIC values of 7.8 μg/mL, 15.6 μg/mL, and 15.6 μg/mL, respectively, with S_Cu@SPIONs and S_Ag-Cu@SPIONs maintaining growth inhibition for longer durations than free sulfadiazine (MIC: 15.6 μg/mL). Similarly, meloxicam-functionalised SPIONs (M_Ag@SPIONs, M_Cu@SPIONs, and M_Ag-Cu@SPIONs) displayed MIC values of 62.5 μg/mL, 62.5 μg/mL, and 31.25 μg/mL, respectively, exhibiting improved efficacy compared to free meloxicam. Overall, this study establishes SPIONs and their metal-modified derivatives as promising candidates in TB drug development. They exhibited dual functionality, acting both as direct antimycobacterial agents and as nanocarriers that enhanced the efficacy of repurposed drugs. Moreover, the study revealed distinct species-specific (Msmeg and Mtb) responses to metal stress. Notably, Mtb required higher nanoparticle concentrations to achieve comparable inhibition observed with Msmeg. This difference is attributable to Mtb’s more robust metal efflux systems and adaptive mechanisms. Doctoral 2026-04-02T06:48:44Z 2026-04-02T06:48:44Z 2026-03 Thesis https://scholar.sun.ac.za/handle/10019.1/135584 en Stellenbosch University 217 pages : ill. application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Badejo, Motunrayo Victoria Mycobacterium tuberculosis metallomics |
| title | Mycobacterium tuberculosis metallomics |
| title_full | Mycobacterium tuberculosis metallomics |
| title_fullStr | Mycobacterium tuberculosis metallomics |
| title_full_unstemmed | Mycobacterium tuberculosis metallomics |
| title_short | Mycobacterium tuberculosis metallomics |
| title_sort | mycobacterium tuberculosis metallomics |
| url | https://scholar.sun.ac.za/handle/10019.1/135584 |
| work_keys_str_mv | AT badejomotunrayovictoria mycobacteriumtuberculosismetallomics |