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

Campylobacter jejuni is the leading cause of bacterial gastrointestinal disease in Canada, with symptoms including watery to bloody inflammatory diarrhea. Infection may also lead to autoimmune disorders such as reactive arthritis, and the neuromuscular paralysis Guillain-Barré Syndrome. The majority of human infections are acquired from agricultural sources because C. jejuni harmlessly inhabits fowl, cattle and pigs. Despite intensive efforts to eliminate the bacterium during food processing, it is found on up to 95% of fresh poultry meat. Adaptation to hostile environments of high osmotic concentration, found in animal hosts and the human body, is a critical feature of the C. jejuni lifecycle, and is necessary for transmission of the disease to humans. We identified a gene for a regulatory protein called Cj1533c that is over-produced under conditions of high osmotic stress. If Cj1533c is absent from C. jejuni, the pathogen is unable to survive osmotic stress. We also discovered that Cj1533c has two functions, the first function may be to control the expression of genes important for stress survival, and the second function may modify important stress proteins to control their activity. Identifying (I) which genes Cj1533c regulates, (II) the proteins that interact with Cj1533c, and (III) genetic mutations that confer osmotic stress tolerance in the absence of Cj1533c, will provide insight into new stress survival mechanisms. Increasing antibiotic resistance, and the high number of C. jejuni infections reported worldwide, necessitates a mechanistic understanding of stress responses for the discovery of next-generation drug or vaccine candidates and pathogen control strategies.