Exploring South African medicinal plants as modulators of the methylerythritol phosphate pathway for antitubercular drug discovery

Title : Exploring South African medicinal plants as modulators of the methylerythritol phosphate pathway for antitubercular drug discovery

Abstract:

The emerging multidrug-resistant Mycobacterium tuberculosis (Mtb) strains necessitates innovative strategies to identify essential metabolic pathways and therapeutic candidates. The Methylerythritol Phosphate (MEP) pathway is crucial for mycobacterial survival, cell wall integrity, and stress adaptation. Because of its essentiality, this pathway represents an important target for pathway-directed drug discovery, particularly through knockdown of key genes. This study evaluated the antimycobacterial activity of selected medicinal plant extracts against an MEP-pathway knockdown strain of Mycobacterium smegmatis, which was used as a surrogate model for M. tuberculosis. The susceptibility of the knockdown strain was compared with that of the wild-type and the empty-insert control strains to determine whether disruption of the MEP pathway increases sensitivity to plant-derived compounds. The study determined the minimum inhibitory concentrations, bioautography, and evaluated the growth-kinetics curves for the MEP-pathway knockdown strain in comparison with the wild-type and empty-insert control following treatment with the plant extracts. Targeted knockdown of a key MEP-pathway gene markedly increased the susceptibility of M. smegmatis to the evaluated plant extracts. For instance, one aromatic plant extract showed a decrease in Minimum Inhibitory Concentration (MIC) from 310 µg/mL in both control strains to 110 µg/mL in the MEP-gene knockdown strain. Several additional extracts also exhibited enhanced activity specifically against the knockdown strain, as reflected by changes in the growth kinetic curves of the tested microorganisms. These observations suggest that the extracts may interfere with MEP-dependent isoprenoi metabolism. These findings highlight the value of pathway-guided screening to identify potential plant-derived inhibitors targeting essential metabolic processes in mycobacteria.

Biography:

Ramokone Florah Mothupi is a dedicated PhD candidate in Microbiology with a strong passion for drug discovery and antimicrobial research. Her work focuses on understanding how medicinal plant–derived compounds can interfere with bacterial resistance mechanisms, contributing to the search for novel therapeutics. She is driven by scientific curiosity, innovation, and a commitment to academic excellence.