CUKPGP: Epidemio- and immunological perspectives and prophylactic potential of Mycobacterium bovis and M. paratuberculosis co-infections in cattle

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Mycobacterium bovis, a relative of the bacterium causing human tuberculosis is the causative agent of bovine tuberculosis. A related bacterium M. avium subsp. paratuberculosis (MAP) causesa chronic wasting enteritis in cattle and is thought to have a role in Crohn's disease in man. Bothbacteria and thier diseases remain major public health and/or economic problems in many countries, including the UK and P.R.China. The incidence of M. bovis infection is well documented whereas information on MAP is poor in many countries. It is likely that mixed infection with these two pathogens occurs with unknown consequences for the progress of both diseases. We have exploited a technology (a DNA-based microarray) that allows simultaneous detection of many micro-organisms in a sample simultaneously. Our assay allows the simultaneous detection of 13 mycobacterial species (including the two mentioned in this proposal), which will be applied in both countries to assess the incidence of infection with the individual pathogens and also of mixed infection.We have also been interested for some time in the stimulation of the innate immune system shortly after infection and the consequences for subsequent infection by related and unrelated pathogens. Innate immunity is the initial host response to infection an is not a learned response but will occur in the same way to many different bacterial types. The presence of intracellular bacteria in the tissues confers a profound resistance for some time after infection against unrelated pathogens. The outcome of this work is the indication that live bacterial vaccines (e.g. live Salmonella vaccines which would not interfere with the standard skin test used for testing individual animals and for surveillance) might be used to confer rapid resistance to mycobacterial infection as an emergency protection measure. There is an indication that this approach might also be used therapeutically in some circumstances and has potential application for controlling human infection..This project will involve (i) use of DNA microarray technology to survey the incidence of mixed and single mycobacterial infections in China and the UK, and (ii) an assessment of the immunological interaction between M. bovis, MAP and Salmonella early in infection and whether this approach might be used to protect against these two mycobacterial pathogens for periods when naïve animals might be exposed to infection.