Molecular Approaches to Investigate the Pathogenesis of, and Prophylaxis for, Mycobacterium Avium Subspecies Paratuberculosis

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 involve culling or removing animals that test positive and are generally ineffective because of sub-optimal diagnostic techniques 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 current vaccines have a number of disadvantages. 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>This programme of work has contributed to our understanding of the molecular mechanisms involved in pathogenesis to promote the development of novel vaccines for M.a.paratuberculosis. Information has been obtained regarding the regulation of identified potential virulence genes of M.a.paratuberculosis and the closely related organism M.avium. A short-term laboratory animal model of infection has been developed that allows rapid assessment of virulence and candidate vaccines and will be an important tool for future research. The model has been successfully used to evaluate the virulence of M.a.paratuberculosis isolates from different host species yielding important epidemiological information. In addition, an effective procedure for typing M.a.paratuberculosis isolates has been developed that will permit epidemiological monitoring and surveillance.