Grant: Project Grant

Infectious diseases are still among the most frequent causes of deaths. Fortunately, antibiotics save millions of lives every year. However, according to the World Health Organization (WHO), antibiotic resistance is a major threat to public health. The rapid spread of antibacterial resistance highlights the need to globally combat this problem. Compounding things, the pace of novel antibiotic discovery has plummeted to a level not seen since the 1940's. Thus, the discovery of novel antibiotics is critical. This project aims to identify novel anti-infective agents that will replace classic and failing antibiotics. Our research focuses on bacterial pathogens that intimately interact with human tissue because current antibiotics do not specifically target these. The focus of this proposal is the bacterium Shigella, which on a global scale is responsible for hundred of millions infections each year. The outcome for roughly 1 million of these cases is death. According to the WHO, Shigella is one of the bacteria for which novel antibiotics are urgently needed. Shigella is a pathogen that lives within human intestinal cells. Normally, human cells can recognize intracellular bacteria and destroy them, however Shigella is capable of evading detection and destruction. This project will identify the mechanisms used by Shigella to hijack human cellular factors. This deeper understanding of Shigella pathogenesis will facilitate the design of novel therapeutics stimulating the host defense and inhibiting Shigella hijacking mechanisms. Because of their specificity, these novel therapeutic strategies will be less prone to resistance than classical antibiotics. As a result, this work will impact both Canadian and global communities, and translation of the acquired knowledge to new treatments will open the door to collaboration between basic scientists and clinicians.