Grant: Operating Grant

The emergence of new and drug-resistant variants of microbial agents of disease (also known as pathogens) represents a challenge to human health. The objective of the proposed research is to understand how these disease-causing entities interact with other microbes and host cells in an attempt to identify novel drug targets for alternative therapies. We are studying Vibrio cholerae, the bacterium that causes cholera - an infection of the small intestine that causes severe watery diarrhea, dehydration, and too often death. While cholera is endemic in many regions of the world causing over 120,000 deaths every year, it is also one of the first diseases that emerge when a country is faced with an economic crisis or a natural disaster, mostly because the health care system and sanitation infrastructure breaks down. The most recent examples are Zimbabwe which experienced a major cholera outbreak in 2009 with 100,000 cases and 4,300 deaths, and Haiti which suffers from the consequences of a major earthquake in early 2010. Cholera then becomes a health threat to those Canadians who travel to these affected regions as relief workers or health professionals. The delivery of poisonous substances (toxins) is a common mechanism bacteria use to cause disease. We have discovered a novel mechanism by which V. cholerae delivers toxins to kill other bacteria as well as eukaryotic cells. We hypothesize that V. cholerae uses this system to cope with competitors in the environment and in the human host where they cause disease. This project is designed to expand our knowledge on how this delivery mechanism contributes to microbial infections. We plan to do this by studying when the toxins are produced, where the toxins go, and what the toxins do in the infected host cell. We anticipate that our findings will help us identify weaknesses that can be exploited therapeutically for the large number of pathogens whose genomes contain the information for this virulence mechanism.