Johne's disease (Paratuberculosis) is a chronic granulomatous enteritis occurring worldwide among wild and domestic ruminants. Worldwide, the disease causes major economic damage, including in the USA and in Israel. The disease is caused by the pathogen Mycobacterium avium sub. paratuberculosis (in short - MAP), a slow growing member of the mycobacteria family, which also includes the human pathogen Mycobacterium tuberculosis. The bacterium infects newborn calves, rarely causes any clinical disease at infection, but instead resides in a dormant state in macrophages, arranged in granulomas. In a significant minority of the infected animals the bacteria undergo "reactivation" and resume active multiplication, which is not contained by the immune system. This reactivation takes place in the lymphatic tissue associated with the small intestine, and causes generalized enteritis, leading to severe inflammatory disease, malabsorption, diarrhea and excretion of bacteria in the feces (which in turn infects other animals). Research into the pathogenesis of the paratuberculosis bacteria is hindered by lack of good genetic tools, difficulties in genetic manipulation of the bacteria, its slow growth and other factors. The lack of knowledge of the important pathogenesis factors also hinders the creation of an effective vaccine – the existing vaccines are composed of inactivated bacteria and lack good efficacy, whereas understanding of pathogenesis factors would enable us to construct effective live attenuated vaccines.