<i>Mycobacterium smegmatis</i> Response to Superparamagnetic Iron Oxide Nanoparticles (SPIONs)

Introduction Tuberculosis, caused by Mycobacterium tuberculosis , remains a major global health challenge worsened by antimicrobial resistance. This study explores the antimycobacterial efficacy of metal-coated superparamagnetic iron oxide nanoparticles (SPIONs) as alternative therapeutic agents. Methods SPIONs were synthesized through chemical co-precipitation and functionalized with metals to create bimetallic (Ag@SPIONs, Au@SPIONs, Cu@SPIONs, Ni@SPIONs) and trimetallic (Ag-Cu@SPIONs, Ag-Ni@SPIONs) nanoparticles. The physicochemical characteristics of the metal-coated SPIONs were assessed using microscopy and spectroscopy techniques. Antimicrobial activity of the nanoparticles against Mycobacterium smegmatis mc 2 155 was evaluated using time-kill kinetic assays. Additionally, differential gene expression analysis was conducted to investigate cellular responses following nanoparticle exposure. Results Transmission electron microscope analysis revealed average particle sizes of 10.28 nm for SPIONs, and 12.51 nm, 17.07 nm, 14.60 nm, 16.18 nm, 14.68 nm, and 15.00 nm for Ag@SPIONs, Au@SPIONs, Cu@SPIONs, Ni@SPIONs, Ag-Cu@SPIONs, and Ag-Ni@SPIONs, respectively, all displaying a predominantly spherical morphology. Antimicrobial testing demonstrated a potency ranking: Ag-Cu@SPIONs (1.95 µg/mL) > Ag-Ni@SPIONs (3.9 µg/mL) > Ag@SPIONs (3.9 µg/mL) > Cu@SPIONs (62.5 µg/mL) > Ni@SPIONs (>62.5 µg/mL). Gene expression analysis revealed that Ag@SPIONs and Ag-Cu@SPIONs induced strong upregulation of heavy-metal detoxification genes, whereas Cu@SPIONs significantly enriched pathways linked to valine, leucine, and isoleucine degradation, and fatty acid and propanoate metabolism. Discussion This study demonstrates that metal-coated SPIONs possess strong antimycobacterial activity and significantly modulate key metabolic and stress-response pathways in Mycobacterium smegmatis . The superior efficacy of Ag-Cu@SPIONs highlights the advantage of metal synergy in enhancing nanoparticle potency. Conclusion Overall, the findings demonstrate that metal-coated SPIONs hold significant promise as alternative antimycobacterial agents. However, comprehensive in vivo studies are required to fully determine their therapeutic effectiveness and safety.