Infection proteomics

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The zoonotic pathogen Leptospira is the causative agent of leptospirosis, a disease of global importance that is acquired by exposure to infectious body fluids and tissues or by direct contact with urine-contaminated soil or fresh water.  Leptospira are a genus of free-living spirochetal bacteria, comprising both environmental and pathogenic species. The pathogenic Leptospira are of particular scientific interest due to their ability to adapt to and grow in a variety of environments, including soil and fresh water. Remarkably, the organisms also have the genetic capacity to resist the contrasting selective pressures of the mammalian host defense system and can attain high numbers in both humans and animals.  Little is currently known about the differential gene and protein expression profiles facilitating Leptospira adaptation to these various milieus.  In this research proposal, we will compare global protein expression profiles of leptospires in the mammalian host.  These studies will provide insight into the leptospiral infection process via analyses at the whole-proteome level.  The overall objective of this research is to assess the protein expression profile of a pathogen during infection; these investigations will constitute the first global protein expression analysis of any pathogen during the infection process.  Information gained from studies performed on our model pathogen, Leptospira, will allow future investigations on additional pathogens that exhibit diverse infection capabilities.  Advances in our understanding of the infection process at the whole proteome scale will significantly contribute to the varied fields of microbiology, bacterial pathogenesis, molecular biology and other disciplines relating to infection and immunity.  In addition, advances made in these studies will directly benefit Canada, since leptospirosis and other diseases caused by pathogenic organisms occur throughout the country.