CSIR-CCMB Study Identifies Potential Tuberculosis Drug Targets

On 10 November 2026, researchers at the CSIR-Centre for Cellular and Molecular Biology (CCMB) in Hyderabad identified weaknesses in Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). The findings may help identify drug targets, but developing medicines will require several more years of research. India accounts for nearly a quarter of global TB cases and about a third of drug-resistant infections.

Mapping the protein transport network

Led by CCMB Director Vinay Kumar Nandicoori, the team mapped the bacterium’s protein export machinery. Joint first authors Priyadarshini Sanyal and Jagadeeshwari Uppada worked with the Institute of Mathematical Sciences, Chennai, led by Areejit Samal, and the Translational Health Science and Technology Institute, Faridabad.

Computational modelling and laboratory experiments identified 92 key components and nearly 200 molecular reactions in the network. These included the general Sec pathway, the Twin-Arginine Translocation (Tat) system and specialised ESX secretion systems.

SecA1 and Tat pathways

Using CRISPR-based gene silencing, researchers reduced activity in the SecA1 and Tat pathways. Bacterial growth fell sharply in laboratory cultures and inside immune cells. Disruption affected the export of more than 100 proteins linked to SecA1 and around 140 linked to Tat. It also damaged the bacterial cell membrane, making it unstable and more permeable.

The findings were published in the peer-reviewed journal Molecular & Cellular Proteomics.

Important Facts for Exams

• Mycobacterial envelope: The mycobacterial outer membrane is rich in mycolic acids and forms a low-permeability barrier that limits entry of many antibiotics.
• Sec transport mechanism: In bacteria, SecA uses ATP to drive largely unfolded proteins through the SecYEG membrane channel, distinguishing Sec transport from Tat export.
• Tat energy source: Tat machinery recognizes signal peptides with a twin-arginine motif and transports folded proteins across the membrane using the proton motive force.
• ESX secretion: Mycobacterial ESX systems are Type VII secretion systems; ESX-1 exports ESAT-6 and CFP-10, proteins implicated in host-cell membrane damage and virulence.