Abstract Description

Tuberculosis remains a major global health concern, exacerbated by the rise of drug-resistant, multidrug-resistant, and extensively drug-resistant strains of Mycobacterium tuberculosis. The effectiveness of conventional antitubercular drugs is diminishing, largely due to their limited ability to penetrate the complex mycobacterial cell wall, which is shaped by the intricate biosynthetic metabolism of M. tuberculosis. Therefore, a comprehensive investigation into the key metabolic pathways that govern the growth and survival of M. tuberculosis could provide critical insights for the discovery and development of more potent antitubercular therapies from diverse sources. This study investigated the key gene in Methylerythritol Phosphate (MEP) pathway of Mycobacterium smegmatis as a potential target for antitubercular drug discovery, using extracts from selected traditional medicinal plants known for their antimicrobial properties. Plant species were chosen based on ethnobotanical significance and extracted using standard phytochemical procedures. The antimycobacterial activity of the extracts was assessed through a serial broth microdilution assay against M. smegmatis strains with reduced expression of a key gene in the MEP pathway. Growth phenotypes were evaluated in both solid and liquid media, while cytotoxicity of the plant extracts was examined using the human monocytic leukemia cell lines (THP-1). The study demonstrated enhanced antimycobacterial activity from the tested plant extracts, with Buddleja saligna and Combretum apiculatum showing particularly notable effects at minimum inhibitory concentrations of 0.31 mg/mL and 0.08 mg/mL, respectively. Phenotypic analysis of the test microorganism revealed disrupted growth patterns, indicating interference with mycobacterial development. Furthermore, the plant extracts exhibited minimal cytotoxicity on the THP-1 cell lines, indicating the safety of the therapeutic use of the extracts from the selected plants. These findings suggest that targeting the MEP pathway with bioactive compounds from traditional medicinal plants presents a promising strategy for the discovery and development of novel antitubercular agents. Further validation through in vivo studies is recommended.