CSIR-CCMB Scientists Identify Novel Drug Targets to Fight Tuberculosis
Biomedical scientists at the CSIR-Centre for Cellular and Molecular Biology in Hyderabad have mapped vital vulnerabilities in the bacterium responsible for causing tuberculosis. The medical discovery offers potential drug development pathways to combat one of the deadliest infectious bacterial diseases worldwide. The scientific breakthrough holds particular relevance for India, which accounts for nearly a quarter of global tuberculosis incidence according to international reports. Health statistics indicate that the country also bears approximately one third of all global drug-resistant tuberculosis infections. Treatment regimens for resistant tuberculosis strains require intensive multidrug therapy administered over multiple consecutive months amid increasing pathogen resistance.
Molecular Architecture and Secretion Networks
The scientific investigation was supervised by center director Vinay Kumar Nandicoori, who directed efforts to map the internal protein export machinery of Mycobacterium tuberculosis. The experimental research was conducted by joint primary investigators Priyadarshini Sanyal and Jagadeeshwari Uppada in collaboration with the Translational Health Science and Technology Institute. Partnering computational teams led by Areejit Samal at the Institute of Mathematical Sciences contributed specialized mathematical modeling frameworks to the analysis. By combining predictive computational algorithms with biological laboratory testing, investigators mapped 92 structural components and nearly 200 distinct molecular reactions within the pathogen. The mapped transport systems incorporated the general Sec pathway, the Twin-Arginine Translocation network, and specialized bacterial ESX secretion mechanisms.
Genetic Silencing and Membrane Destabilization
Laboratory teams focused analytical testing on two central secretion channels designated as SecA1 and Tat to assess their necessity for bacterial viability. Researchers deployed targeted CRISPR-based gene-silencing technologies to intentionally suppress the biological activity of both transport channels. Following genetic suppression, bacterial reproduction declined sharply across both isolated laboratory culture media and colonized host immune cells. Analysis conducted by Priyadarshini Sanyal revealed that molecular disruption impaired the export of over 100 proteins in the SecA1 pathway and around 140 proteins within the Tat network. Structural imaging verified that inhibiting secretion disrupted bacterial cell membranes, inducing physical permeability and causing vital cellular proteins to leak outward. In August 2024, researchers identified the cell-wall biosynthesis enzyme GlmM as an essential target against Mycobacterium tuberculosis using CRISPR interference-mediated gene silencing, according to National Library of Medicine.
Research director Nandicoori explained that the observed structural defects establish an intimate dependency between protein transport and outer envelope stability. Scientific findings detailing the secretion architecture were published in the international peer-reviewed journal Molecular and Cellular Proteomics. Translating these biological targets into viable clinical pharmaceutical treatments will require several more years of research. India accounts for about 25% of global TB cases, roughly 28% of global TB deaths in 2024, and about 32% of global multidrug-resistant and rifampicin-resistant cases, according to The Cavalier.