Research Projects

Mycobacterium tuberculosis (Mtb) is a deadly disease that infects a significant portion of the global population annually. Mtb uses various mechanisms to survive, including the use of cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CGL) enzymes from the transsulfuration pathway. The Mtb EMSH-reduced subpopulation is highly drug-tolerant, and these enzymes are overexpressed in this subpopulation, providing drug tolerance to Mtb. These enzymes regulate the conversion of homocysteine to cysteine biosynthesis and release hydrogen-di-sulfide (H₂S), which protects Mtb from oxidative stress by scavenging reactive oxygen species (ROS). However, there is no structural study of the full-length hCBS and the heme-binding domain. To study the inhibition mechanism of MtbCBS, which is unable to inhibit the hCBS enzyme, researchers are investigating existing and novel drug molecules. This will help develop alternative therapeutic strategies and novel inhibitors against Mtb, which has no effect on host cells. Cryo-EM-based structural and functional studies with substrates and inhibitors will help understand the bacterial survival strategy inside host cells.