Genomic Polymorphisms forMycobacterium aviumsubsp.paratuberculosisDiagnostics

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Abstract
Mycobacterium aviumsubsp.paratuberculosisis an emerging pathogen of mammals and is being actively investigated as a possible zoonotic agent. The lack of reliable diagnostic assays has hampered rational assessment of the prevalence of this organism in humans and animals. We have used a comparative genomic approach to reveal genomic differences betweenM. aviumsubsp.paratuberculosisand its close relativeM. aviumsubsp.avium, a highly prevalent environmental organism. From computational and DNA microarray-based study of two prototype strains,M. aviumsubsp.aviumstrain 104 andM. aviumsubsp.paratuberculosisstrain K10, we have uncovered two types of large sequence polymorphisms (LSPs): those present in the former but missing in the latter (LSPAs) and those only present in the latter (LSPPs). We examined the distribution of 3 LSPAs and 17 LSPPs across a panel of 383M. aviumcomplex isolates in order to determine their potential utility for the development of accurate diagnostic tests. Our results show that the absence of LSPA8 is 100% specific for the identification ofM. aviumsubsp.paratuberculosis. Of the 17 LSPPs, 10 regions were not specific forM. aviumsubsp.paratuberculosiswhile 7 were shown to be highly specific (>98%) and, in some cases, highly sensitive as well (up to 95%). These data highlight the need to evaluate these regions across a diverse panel of clinical and environmental isolates and indicate the LSPs best suited forM. aviumsubsp.paratuberculosisdiagnostics.

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