Grant: Banting Postdoctoral Fellowship Program

Mycobacterium tuberculosis (TB), once considered a disease of the past, is making a significant comeback. Until the early 1990s, first-line anti-TB drugs were highly effective. TB has since reemerged in the past decade by acquiring multiple mechanisms of drug resistance and, once again, threatening world healthcare. Latest numbers in Canada show an increase in infections of 4 % per year, with Aboriginal populations having seen no drop in infection in 30 years and over twice as much at risk. TB is killing more than 2 million people every year with estimates of 9 million each year. The new multidrug resistant strains of TB are now surviving first-line antibiotics, requiring patients to undergo a second round of antibiotics. These second-line antibiotics are much tougher on the patient and are leading to further antibiotic resistance. Several countries are now reporting extensively drug-resistant TB (XDR-TB) strains that are effectively untreatable. Due to the highly infectious nature of TB, these new drug-resistant strains could easily become the next global pandemic. For this reasons, better understanding of TB operation is needed to further anti-TB efforts. One such anti-TB target is the type VII secretion system (T7SS), this system is used by Mycobacteria, such as TB, to transport the invasion tools across the TB's outer membrane necessary to invade and infect a target cell. This research, aims to elucidate a high-resolution molecular structure of the T7SS - by understanding the three dimensional structural of the complex, it can be understood how it interacts with specific targets, and crucially how to inhibit it. By stopping the TB from being infectious we could avert a global pandemic and perhaps save millions of lives, both in Canada and worldwide.