CSIR-CCMB scientists discover new drug targets to tackle Tuberculosis

Scientists at the CSIR-Centre for Cellular and Molecular Biology (CCMB) have identified critical structural weaknesses in Mycobacterium tuberculosis, the bacterium responsible for Tuberculosis (TB). By mapping the pathogen's intricate protein export machinery, the research team revealed fresh targets that could lead to new treatments against drug-resistant strains of the disease.

The landmark study was led by CCMB Director Vinay Kumar Nandicoori alongside joint lead authors Priyadarshini Sanyal and Jagadeeshwari Uppada. Published in the journal Molecular & Cellular Proteomics, the findings highlight how the bacterium transports proteins required to grow, survive and evade human immune defenses.

Using a combination of laboratory experiments and computational modelling, the team mapped 92 key components and nearly 200 molecular reactions within the pathogen's transport network. The research focused heavily on two main protein export pathways: the SecA1 system and the Twin-Arginine Translocation (Tat) system.

Comparing the targeted bacterial pathways

To test whether these pathways are essential, the researchers used CRISPR-based gene-silencing techniques to dial down their activity. The intervention caused a sharp drop in bacterial growth both in culture dishes and inside human immune cells.

Disrupting these delivery channels also caused direct physical damage to the bacterial envelope. The outer wall became unstable and leaky, allowing internal proteins to spill out into the surrounding environment. Dr Nandicoori noted that these structural changes underscore the direct link between protein secretion and cell envelope stability, which allows the bacterium to resist existing medications.

The project brought together multi-institutional scientific strength across India. Computational analysis was led by Areejit Samal at the Institute of Mathematical Sciences in Chennai, alongside contributions from the Translational Health Science and Technology Institute in Faridabad.

According to the World Health Organisation's Global TB Report 2025, India carries nearly a quarter of global TB cases and around a third of drug-resistant infections. By uncovering the internal mechanics of the pathogen, Indian researchers are placing the country at the forefront of the global push for next-generation antibiotics.