CSIR-CCMB mapped Mycobacterium tuberculosis protein export and found two essential pathways in lab tests

A team at the CSIR-Centre for Cellular and Molecular Biology (CCMB) in Hyderabad has mapped the protein export machinery of Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, and identified weaknesses in it, reports The Hindu Sci-Tech on 10 November 2026 thehindu.comThe Hindu Sci-Techthehindu.comOpen source ↗. The study was led by CCMB Director Vinay Kumar Nandicoori. Joint first authors were Priyadarshini Sanyal and Jagadeeshwari Uppada.

The researchers worked with the Institute of Mathematical Sciences, Chennai, led by Areejit Samal, and the Translational Health Science and Technology Institute, Faridabad. The results were published in the peer-reviewed journal Molecular & Cellular Proteomics.

Mapping the protein transport network

The team combined computational modelling with laboratory experiments. They identified 92 key components and nearly 200 molecular reactions in the bacterium's protein transport network. The network includes the general Sec pathway, the Twin-Arginine Translocation (Tat) system and the ESX secretion systems, which are specific to this group of bacteria.

The process governs how the pathogen moves proteins within and outside its cells and is essential for its growth, survival and ability to cause disease thehindu.comThe Hindu Sci-Techthehindu.comOpen source ↗. "Protein secretion acts like a delivery system inside the bacterium and is vital for its survival," said Uppada.

Silencing SecA1 and Tat

The authors focused on two pathways, SecA1 and Tat, and reduced their activity with CRISPR-based gene silencing. Bacterial growth declined sharply both in laboratory cultures and inside immune cells, which indicates that both pathways are essential for the pathogen.

According to Sanyal, disrupting these systems affected the export of more than 100 proteins in the SecA1 pathway and around 140 proteins linked to the Tat system. The researchers also observed structural damage to the bacterial cell membrane, which became unstable and more permeable. Proteins that normally stay inside the bacterium leaked into the surrounding environment.

Nandicoori said these changes show a close link between protein secretion and the maintenance of the bacterial cell envelope, a factor in TB's persistence and resistance to treatment thehindu.comThe Hindu Sci-Techthehindu.comOpen source ↗.

Context and stage

The article cites the World Health Organisation's Global TB Report 2025: India accounts for nearly a quarter of global TB cases and about a third of drug-resistant infections. Treatment requires a combination of antibiotics taken over several months, and resistant strains make it harder.

The findings could help researchers identify new drug targets. Turning them into effective medicines will require several more years of research.