Mycobacterium avium subsp. paratuberculosis in Veterinary Medicine

Abstract

Mycobacterium avium subsp. paratuberculosis (basonym M. paratuberculosis) is the etiologic agent of a severe gastroenteritis in ruminants known as Johne's disease. Economic losses to the cattle industry in the United States are staggering, reaching $1.5 billion annually. A potential pathogenic role in humans in the etiology of Crohn's disease is under investigation. In this article, we review the epidemiology, pathogenesis, diagnostics, and disease control measures of this important veterinary pathogen. We emphasize molecular genetic aspects including the description of markers used for strain identification, diagnostics, and phylogenetic analysis. Recent important advances in the development of animal models and genetic systems to study M. paratuberculosis virulence determinants are also discussed. We conclude with proposals for the applications of these models and recombinant technology to the development of diagnostic, control, and therapeutic measures.

FIG. 1

IS900 inserts in a target gene of M. paratuberculosis in an orientation-specific manner. A putative target gene of M. paratuberculosis is illustrated as a hatched line, with the corresponding upstream and downstream sequences of the genome shown as open lines. The IS900 insertion consensus sequence from Green et al. (137) and Bull, et. al. (29) is italicized and is denoted in the 3′ to 5′ direction in the illustration. An asterisk indicates the site of IS900 insertion (defines insertion in the hed orientation, according to the nomenclature of Bull et al. [29]). The RBS for the putative chromosomal target gene is represented by an open square, and its corresponding promoter (P) is shown as a black oval. A black line represents the IS900 sequence. The DNA sequences for the putative target gene RBS and its start codon are boxed. The replacement RBS at the 3′ end of IS900 is shown as a vertically striped square, and a horizontally striped square represents the RBS for the p43 gene. Small arrows above or below the RBS squares indicate the direction of translation. Black arrows represent the putative transposase (p43) and hed structural genes encoded for in IS900.

FIG. 2

Sequence comparison of the 5′ ends of IS1626 and IS900. The sequences of the primer sets for M. paratuberculosis IS900 published by Vary et al. (305) (Vary primers) and Millar et. al. (202) (Millar primers) are shown in boldface type. The Millar primers (Millar F and Millar R) are represented by solid arrows, and the Vary primers (Vary F and Vary R) are represented by dashed arrows.