The cell envelope of Mycobacterium tuberculosis is one of the bacterium’s most formidable defenses. Unlike the cell walls of many other bacteria, the mycobacterial envelope is a complex, lipid-rich structure that serves as an exceptionally effective barrier against antibiotics, host immune responses, and environmental stressors. This highly specialized envelope is a major factor in the pathogen’s virulence and persistence, making M. tuberculosis notoriously difficult to eliminate and contributing to the challenges of treating tuberculosis.
Through her UNU-BIOLAC-supported fellowship at the European Molecular Biology Laboratory (EMBL) in Hamburg, Germany, Chiara Coronel Cappellari continued her research on one of the molecular machines responsible for producing the lipid building blocks that form this protective envelope. Her research focused on an essential enzyme complex involved in the biosynthesis of key lipid precursors required for M. tuberculosis survival and pathogenicity.
Using state-of-the-art cryo-electron microscopy (cryo-EM), Chiara worked to reveal the three-dimensional architecture of the ACCase 5 complex at near-atomic resolution. She aimed to identify structural vulnerabilities that could be exploited for drug development, helping to the evetual design of compounds that selectively disrupt these bacterial systems without affecting human cellular machinery. Such drugs could effectively weaken or disable one of the pathogen’s primary defenses, making it more vulnerable to treatment and immune clearance.
Tuberculosis remains one of the world's most important infectious diseases, causing millions of new infections each year and continuing to pose a major global health challenge. The emergence of multidrug-resistant and extensively drug-resistant strains has further increased the urgency of developing new therapeutic strategies that act on previously unexplored targets.
The successful completion of this fellowship was made possible through the collaboration of leading research institutions in Latin America and Europe. UNU-BIOLAC warmly acknowledges the guidance and support provided by Dr. Matthias Wilmanns of the European Molecular Biology Laboratory (EMBL), Hamburg, Germany, as well as Dr. Lautaro Diacovich and Dr. Hugo Gramajo of the Institute of Molecular and Cellular Biology of Rosario (IBR-CONICET), Argentina. Their mentorship, together with the institutional support of EMBL Hamburg and IBR-CONICET, was instrumental in advancing this important research and fostering international scientific collaboration.
