Pathogenesis of Mycobacterium Avium Subspecies Paratuberculosis Infections

Paratuberculosis (Johne’s disease) is a fatal chronic enteritis of ruminants caused by Mycobacterium avium subspecies paratuberculosis and some strains of M.avium. The disease is endemic and responsible for significant economic losses. Current control measures are generally ineffective because they depend on culling or removing animals that test positive in sub-optimal diagnostic tests that lack specificity. In addition, such an approach is economically unacceptable for low value animals, such as sheep or goats, or where endemic disease or reservoirs of infection prevail. Vaccination offers a more acceptable alternative approach but vaccine development for paratuberculosis is hindered by the lack of information regarding the molecular basis for pathogenesis and the inability to pragmatically develop new vaccines by directed mutagenesis. <P>

The objective of this programme of work is to improve our understanding of the molecular mechanisms involved in pathogenesis to promote the development of novel vaccines for M.a.paratuberculosis. Specific aims are to improve our knowledge of the regulation of potential virulence genes and develop a short-term laboratory animal model of infection that will allow rapid assessment of virulence and candidate vaccines.