Scientists Find New Weaknesses in Tuberculosis Bacterium

Scientists at the CSIR-Centre for Cellular and Molecular Biology in Hyderabad have found key weaknesses in the bacterium that causes Tuberculosis. This discovery could help researchers build new medicines to fight the infectious disease.

The Research

Led by CCMB Director Vinay Kumar Nandicoori, the team mapped the protein export machinery of Mycobacterium tuberculosis, the germ responsible for TB. Joint first authors Priyadarshini Sanyal and Jagadeeshwari Uppada carried out the research along with scientists from the Institute of Mathematical Sciences in Chennai and the Translational Health Science and Technology Institute in Faridabad. The team used computer models and lab tests to find 92 key parts and nearly 200 molecular reactions in the bacterium's protein transport network. These included the Sec pathway, the Tat system, and the ESX secretion systems.

Lab Results

The researchers used CRISPR-based gene-silencing technology to lower the activity of the SecA1 and Tat pathways. Bacterial growth dropped sharply both in lab cultures and inside immune cells. Stopping these systems blocked the export of more than 100 proteins in the SecA1 pathway and about 140 proteins linked to the Tat system. This caused physical damage to the bacterial cell membrane, making it unstable and leaky.

Context

India carries a heavy load of the global disease burden, making new treatments a priority for public health experts. Drug-resistant strains of TB make current long-term antibiotic treatments very difficult for patients. While these lab results point the way toward future medicines, turning this discovery into actual drugs will take several more years of scientific study.