Grant: Project Grant - Priority Announcement: Infection and Immunity

Despite the availability of antibiotic drug treatment for more than 50 years, almost 2 million people globally still die from tuberculosis (TB) each year. In particular, the spread of multidrug resistant (MDR) forms of Mycobacterium tuberculosis is one of the major obstacles that is fueling this ongoing TB epidemic and there are 500,000 new MDR-TB cases recorded worldwide every year! The act of acquiring genetic mutations that lead to antibiotic resistance has additional "fitness" costs that place a substantial burden on the M. tuberculosis cell. As such, the goal for this proposal is to apply a multi-disciplinary approach that combines chemical-genetics and large-scale bacterial genomics to identify these critical weaknesses that are inherent to the antibiotic resistant bacteria. In turn, the results of our work will pave the way for the development of novel "resistance-breaking" compounds that can be added to our current drug-treatment regimens in order to target the pathways that specifically support the evolution and maintenance of antibiotic resistance. Overall, our program affords a unique opportunity to extend the life and usability of the currently available first-line TB drugs - including Rifampicin and Isoniazid - that have, in many cases, been rendered practically useless in the face of drug resistant forms of TB.