CSIR-CCMB Scientists Identify New Targets to Fight Tuberculosis

According to a report in The Hindu newspaper, a team of scientists at the CSIR-Centre for Cellular and Molecular Biology (CCMB) has discovered critical vulnerabilities in the bacteria that cause tuberculosis (TB). This discovery could pave the way for developing new treatments against one of the world's deadliest infectious diseases. According to the World Health Organization's Global TB Report 2025, this finding holds special significance for India, as India accounts for nearly a quarter of global TB cases and about a third of drug-resistant infections.

Under the leadership of CCMB Director Vinay Kumar Nandikuri, the research team mapped the protein export system of Mycobacterium tuberculosis (Mtb), the bacterium responsible for TB. The study shed light on how the pathogen transports proteins inside and out of its cells, a process essential for its growth, survival, and ability to cause disease. This research was conducted by joint first authors Priyadarshini Sanyal and Jagadeeswari Uppada in collaboration with scientists from the Institute of Mathematical Sciences, Chennai (led by Arijit Samal) and the Translational Health Science and Technology Institute, Faridabad.

Using a combination of computational modeling and laboratory experiments, the researchers discovered 92 key components and nearly 200 molecular reactions involved in the bacterium's protein transport network. These included the general Sec pathway, the twin-arginine translocation (TAT) system, and specialized ESX secretion systems unique to this genus of bacteria. According to Dr. Uppada, protein secretion inside the bacterium acts like a delivery system and is crucial for its survival. The team focused on two main secretion pathways, SecA1 and Tat, using CRISPR-based gene-silencing technology to reduce their activity. The results were very clear, showing a sharp decline in bacterial growth in both laboratory cultures and immune cells, proving that both pathways are essential for the survival of the pathogen.

Dr. Priyadarshini Sanyal stated that further analysis revealed that disrupting these systems affected the export of over 100 proteins in the SecA1 pathway and approximately 140 proteins associated with the Tat system. The researchers also observed structural damage to the bacterial cell membrane, which made it unstable and more permeable. Proteins that normally stay inside the bacterium began leaking into the surrounding environment. Dr. Nandikuri stated that these changes highlight the close relationship between protein secretion and bacterial cell envelope maintenance, which is a major factor behind TB persistence and resistance to treatment.

These findings were published in the peer-reviewed journal Molecular & Cellular Proteomics, which could help researchers identify new drug targets, although translating this discovery into effective drugs will still take several more years of research.