Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Most E. coli strains are not harmful, but some have acquired genes that make them a serious health concern. These virulence genes encode different traits, such as the ability to produce toxins, protect pathogens from the immune system, or provide antibiotic resistance. The most serious pathogens emerge when multiple virulence genes are combined. An example of a particularity dangerous E. coli strain recently emerged in Germany (May 2011). Over 4000 people were infected and at least 50 died. Smaller outbreaks, like the contaminated beef from a slaughter house in Alberta (September 2012) continue to occur. In addition to causing severe illnesses, these incidents can have a significant economic impact. When outbreaks of bacterial disease occur, rapid containment is essential and antibiotic treatment may be required. Further, the emergence of multi-drug resistant bacteria, including the German E. coli strain, highlights the need for novel antibiotic research. My work focuses on the protein Etk (E. coli Tyrosine Kinase), a potential target for antibiotic development. Within E. coli, Etk confers resistance to the antibiotic polymyxin B and regulates assembly of the capsule, an outer layer which protects bacteria from the human immune system. Proteins with a high degree of similarity to Etk also control capsule formation in other pathogens, including pneumonia and "superbugs", which cause serious hospital outbreaks. My research will yield a thorough understanding of Etk's structure and function. This knowledge will be applied to the design of new antibiotics with a unique mechanism of action. Inhibiting Etk could prevent formation of the capsule, thereby increasing the effectiveness of the immune system and current antibiotics. The inhibitors developed in this project may lead to new drugs with the potential to treat a broad range of bacterial infections, including serious pathogens that continue to evolve.