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Bacteria of the genus Mycobacterium are gram-positive, acid- fast organisms that include a number of significant human and animal pathogens. Mycobacterium avium subsp. paratuberculosis (basonym M. paratuberculosis) is the etiological agent of a severe gastroenteritis in ruminants, known as Johne’s disease. H. A. Johne and L. Frothingham initially reported the disease in Germany in 1894. However, it was not until 1910 that F. W. Trowt successfully fulfilled Koch’s postulates by growing M. paratuberculosis in the laboratory and reproducing the disease in experimentally infected cattle (46, 148). Johne’s disease is prevalent in domestic animals worldwide and has significant impact on the global economy (290). Its influence in the United States alone is staggering, causing an estimated loss of $1.5 billion to the agriculture industry every year (279). It is considered to be one of the most serious diseases affecting dairy cattle (200). However, accurately assessing losses in productivity and profit at the level of an individual herd is difficult, making it likely that the impact of this disease is underestimated nationwide (165, 223). Nonetheless, a Johne’s disease regression model estimates this loss to be from $40 to $227 per cow inventoried per year, based on the percentage of culled cows with clinical signs (219).