Research Projects

Tuberculosis (TB) remains a leading cause of death worldwide, with Mycobacterium tuberculosis (M.tb) being the causative agent. The SARS-COV2 infection has slowed the fight against TB, with around 10 million people affected in 2020, with 26% from India. Directly Observed Treatment Short-course (DOTS) therapy is the only available treatment, but it takes a long time. Mesenchymal Stem Cells (MSCs) are infected with M.tb and promote metabolic reprogramming in M.tb bacteria, causing massive lipid synthesis and activating quiescence genes. MSCs also promote dormancy and drug tolerance in the bacteria. Molecular interactions between hosts and the pathogen are elusive, leading to dormancy in TB. A new treatment modality that simultaneously eliminates dormant bacteria and actively replicates M.tb is needed. This proposal aims to identify targets from MSCs infected with M.tb H37Rv compared to BCG for designing a small molecule inhibitor of dormancy. RNA sequencing analysis will be performed to identify differentially druggable genes from MSCs infected by virulent M.tb strains and compare them with an avirulent strain of Mycobacteria. Genetic analysis will identify the pathway that helps acquire dormancy, and a small molecule inhibitor will be incorporated with conventional antibiotics to evaluate if treatment length is shortened and achieved sterile clearance in a murine model of TB.