Research

Life Sciences & Biotechnology

Title :

Understanding the role of HspX protein from Mycobacterium tuberculosis in translation regulation: its implication in structure based drug design

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Prem singh Kaushal, Regional Centre For Biotechnology, Faridabad, Haryana

Timeline Start Year :

2023

Timeline End Year :

2026

Contact info :

Equipments :

Details

Executive Summary :

Mycobacterium tuberculosis (Mtb) is a major cause of Tuberculosis (TB), the most deadly bacterial disease worldwide. In 2020, TB killed nearly 1.5 million people and was the second leading infectious killer after COVID-19. India remains the highest TB burden country, with 0.5 million deaths from TB-related diseases in 2020. Mtb has a unique mechanism to establish a latent tuberculosis infection (LTBI), the dormancy state, which affects one-third of the world's population. Current drugs have proven inefficient in eradicating TB in latent lesions, and the emergence of multi-drug resistant Mtb strains has increased the alarm. TB treatment requires 3-4 medications for six months or more, while treating drug-resistant TB requires up to 24 months with expensive and toxic medicines. The long duration of chemotherapy treatment may be one reason for the unsuccessful eradication of TB from society. The Mtb processes a small heat shock protein, HspX, which is regulated by DosR regulon and overexpressed up to 87 fold in different stresses. HspX is required for Mtb to survive in mice and macrophages, and its overexpression in acute tuberculosis infection acts as a virulence factor. HspX has been proposed as a promising therapeutic target in combination with traditional antibiotic therapy to shorten chemotherapy treatment and reduce the chance of disease relapse. The molecular mechanism of HspX functioning remains unknown, and no structure of HspX is available. The study proposes determining the cryo-EM structure of the ribosome in complex with HspX protein, performing structure-based drug design, in-vitro screening for potential inhibitors, and growth inhibition testing in a mouse model system.

Total Budget (INR):

42,60,859

Organizations involved

Implementing Agency :

Regional Centre For Biotechnology, Faridabad, Haryana

Funding Agency :

Anusandhan National Rsearch Foundation (ANRF)/science and Engineering Research Board (sERB)

Source :

Anusandhan National Research Foundation/science and Engineering Research Board (sERB), DsT 2023-24

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