Research

Life Sciences & Biotechnology

Title :

Investigating the role of MarR family of transcriptional regulators in antibiotic resistance, stress adaptation, and pathogenesis of Mycobacterium tuberculosis

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Bhupinder Singh Bharadwaj, Translational Health Science And Technology Institute, Haryana

Timeline Start Year :

2023

Timeline End Year :

2025

Contact info :

Details

Executive Summary :

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is the second leading cause of deaths due to a single infectious agent, with India sharing the highest burden of worldwide TB infection. The emergence of drug-resistant strains is further exacerbating the global TB problem, with around 7,00,000 deaths per year due to drug-resistant diseases, and around 2,30,000 deaths due to multi-drug resistant tuberculosis. Mtb is a highly successful intracellular pathogen due to its ability to survive and persist under various environmental conditions. To persist, Mtb employs several DNA-binding transcriptional regulators (TRs) to sense external signals and reprogram its transcriptional machinery. The MarR family of TRs, named after MarR (Multiple antibiotic resistance Regulator) from Escherichia coli, share a characteristic wHTH motif that allows them to bind cognate DNA and usually repress the expression of downstream genes. These TRs are involved in regulating diverse physiological processes, including stress responses and virulence. The Mtb genome harbors eight genes (Rv0042c, Rv0880, Rv2011c, Rv1049, Rv2327, Rv0737, Rv2887, and Rv1404) that share homology with the MarR family of TRs. However, essential biochemical and functional characterization studies on these TRs are still elusive. Proposed experiments aim to identify the regulon of the MarR family of TRs and understand their contribution to disease pathogenesis and antimicrobial resistance development in Mtb.

Organizations involved