PhD conferral Diana Mendes Freire
Aula, Vrije Universiteit Amsterdam
Structural insights in Mycobacterium tuberculosis proteins: from secretion chaperones to toxin-antitoxin systems
Diana Mendes Freire
Prof. W. Bitter, copromotors Dr A. Parret, Prof. M. Wilmanns
Amsterdam Institute for Molecules, Medicines and Systems
The tuberculosis disease (TB) is currently the most deadly infectious disease in the world. It is spread through the air and is caused by the deadly bacterium Mycobacterium tuberculosis.
The active form of TB can usually be controlled with a cocktail of different antibiotics, but the treatment takes a long time and often causes serious side effects. In addition, there is a worrying increase in the number of antibiotic-resistant strains of M. tuberculosis. For these reasons, other anti-TB strategies need to be discovered.
The focus of Diana Mendes Freire’s PhD thesis is on two of the highly complex pathogenic and virulence mechanisms developed by M. tuberculosis: the type VII secretion system, that mediates the secretion of virulence factors, and secondly, toxin-antitoxin systems that are thought to contribute to the ability of M. tuberculosis to persist in the human host.
Proteins involved in these two systems, such as secreted targets, respective chaperones and toxin-antitoxin protein complexes were functionally and structurally characterized using a different array of techniques. In particular, a novel toxin-antitoxin system is presented. This encodes for a cidal toxin which targets one of the most essential metabolites in living cells, NAD+, in a not yet described mechanism. The study here presented opens new avenues for anti-tuberculosis research and antimicrobial drug development.