Molecular mechanisms of carbohydrate uptake in Mycobacterium tuberculosis (360G-Wellcome-104193_Z_14_B)

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB) and is now the leading cause of death from a single infectious agent in the world, killing more people world-wide than HIV and malaria. With the escalation of drug-resistant TB infections we urgently need to develop novel strategies and interventions to control the growing TB global epidemic. To enable this, we need a more detailed understanding of the fundamental biology of Mtb. Mtb is an unusual pathogen that has the exceptional ability to survive within the human host for decades. However the energy sources that Mtb uses within this nutrient-poor environment and the mechanisms involved in their transport are poorly understood. The overarching aim of this project is to use a multidisciplinary approach combining chemistry, biochemistry and microbiology to determine i) which carbohydrates are (re)used by Mtb, ii) how they are (re)used and iii) the molecular mechanisms involved in these processes. This project will provide key insights into carbohydrate uptake/recycling and metabolism by Mtb and assign physiological function to the proteins involved. Altogether, these results will generate important mechanistic insights into the survival of this global pathogen and validate whether these pathways represent therapeutic/diagnostic targets.