CSIR-CCMB team identifies potential new targets to fight tuberculosis

CSIR-CCMB Director Vinay Kumar Nandicooir with fellow researchers Priyadarshini Sanyal and Jagadeeshwari Uppada | Photo credit: BY ARRANGEMENT

A team of scientists from the CSIR-Centre for Cellular and Molecular Biology (CCMB) has identified critical vulnerabilities in the bacterium that causes tuberculosis (TB), a finding that could pave the way for the development of new treatments against one of the world’s deadliest infectious diseases.

The discovery is particularly significant for India, which accounts for nearly a quarter of the world’s TB cases and about a third of drug-resistant infections, according to the World Health Organization. Global TB Report 2025. Drug-resistant TB remains a major public health problem, as treatment requires a combination of antibiotics taken over several months and is increasingly difficult due to the emergence of resistant strains.

A research team led by CCMB Director Vinay Kumar Nandicoori has mapped the protein export mechanism of Mycobacterium tuberculosis (Mtb), the bacterium responsible for TB. The study sheds light on how the pathogen transports proteins inside and outside its cells, a process essential for its growth, survival and ability to cause disease.

The research was conducted by joint first authors Priyadarshini Sanyal and Jagadeeshwari Uppada in collaboration with scientists from the Institute of Mathematical Sciences, Chennai, led by Areejit Samal, and the Translational Institute for Science and Technology, Faridabad.

Using a combination of computational modeling and laboratory experiments, the researchers identified 92 key components and nearly 200 molecular reactions involved in the bacterial protein transport network. These included the general Sec pathway, the Twin-Arginine Translocation (Tat) system, and specialized ESX secretion systems unique to this group of bacteria.

“Protein secretion acts as a transport system inside the bacterium and is vital for its survival,” Dr Uppada said. The team targeted two major secretory pathways, SecA1 and Tat, using CRISPR-based gene silencing technology to reduce their activity. The results were remarkable: bacterial growth plummeted both in laboratory cultures and inside immune cells, demonstrating that both pathways are necessary for pathogen survival.

Dr. Priyadarshini Sanyal reported that further analysis revealed that disruption of these systems affected the export of more than 100 proteins in the SecA1 pathway and about 140 proteins associated with the Tat system. The researchers also observed structural damage to the bacterial cell membrane, making it unstable and more permeable. Proteins that normally remain inside the bacterium began to leak into the environment.

Dr. Nandicoori said these changes highlight the close link between protein secretion and the maintenance of the bacterial cell envelope, a key factor behind TB persistence and resistance to treatment. The findings, published in the peer-reviewed journal Molecular & Cellular Proteomics, could help researchers identify new drug targets, although translating the discovery into effective drugs will require several more years of research.

Published – 10 Nov 2026 08:49 IST