Applying recombinant technologies to define the secretome of M.a. paratuberculosis for the discovery of potential immunogens and diagnostic reagents

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Johne's disease (JD) is an incurable chronic and wasting disease affecting ruminant animals such as cows, goats, sheep elk and deer. Animals become infected by eating live Mycobacterium avium subspecies paratuberculosis (or MAP) bacteria in food, water or milk. JD affects herds in all regions of Canada with up to 40% of dairy herds reporting an infected animal. Herds with infected animals suffer very significant economic looses from decrease in milk production, fertility and increased culling of sick animals. There is also concern regarding the possible association between MAP and some cases of Crohn's disease in humans. These concerns will continue until there is definitive proof against such a link but it would be devastating to the cattle industry if such link were established. Currently there are no vaccines that protect animals against infection and no treatments that prevent or reduce MAP shedding in feces and milk. However, JD can be controlled by stopping the cow-to-cow spread of MAP and this goal can achieved by identifying and removing infected animals before they start shedding the bacterium. However, the current diagnostic tests lack the sensitivity and specificity to detect animals with early stage (or subclinical) disease. To develop such tests, research effort is needed to build on our understanding of the biology and genetics of MAP bacteria and to discover MAP components that can be used to design MAP-specific diagnostic assays and possibly vaccines. To date only a few MAP proteins have been identified and fully characterized. The purpose of our study is to use current recombinant technologies to characterize the proteins secreted by MAP. Secreted proteins make first contact with the host, determine the course of infection and contain the antigens recognized by the host immune system to induce antibody and cell mediated responses. Characterizing secreted proteins also has practical application in the discovery of novel reagents for profiling host immune responses, diagnosis of infection, and differentiation between vaccinated and infected hosts.