Host tropism in the Mycobacterium tuberculosis complex: the role of the secreted protein MPB70 (360G-Wellcome-102395_Z_13_Z)

Tuberculosis (TB) is the most deadly human bacterial disease in the world, killing over 1.5 million people annually and with a reservoir of 2 billion latently infected individuals. Allied to this, tuberculosis in animals is a global threat to public health and animal welfare. The human TB strain Mycobacterium tuberculosis shares 99.95% nucleotide sequence identity with thebovine strain Mycobacterium bovis, but the molecular bases for host preferenceare currently unknown. The aim for this project is to identify host tropic proteins from the Mycobacterium tuberculosis complex (MTBC). We will focus our study on MPB70, aprotein constitutively secreted at high levels by M.bovis, as we have preliminary data to show that this protein modulates cellular immune responses. We will build on these data using both conventional techniques and global transcriptome analyses via RNA-Seq. For the latter, we will develop novel approaches in data analysis in the area of longitudinal cluster analysisto define the mechanism of action of this protein in mixed cellular