Comprehensive insights in the mycobacterium avium subsp. Paratuberculosis genome using new wgs data of sheep strain jiii-386 from Germany

Abstract

Mycobacteriumavium(M.a.) subsp. paratuberculosis(MAP)-theetiologic agent of Johne's disease-affects cattle, sheep, andother ruminants worldwide. To decipher phenotypic differences among sheep and cattle strains (belonging to MAP-S [Type-I/III], respectively, MAP-C [Type-II]), comparative genome analysis needs data fromdiverse isolates originating fromdifferent geographic regions of the world. This study presents the so far best assembled genome of a MAP-S-strain: Sheep isolate JIII-386 from Germany. One newly sequenced cattle isolate (JII-1961, Germany), four published MAP strains of MAP-C and MAP-S from the United States and Australia, and M. a. subsp. hominissuis (MAH) strain 104were used for assembly improvement and comparisons. All genomeswere annotated by BacProt and results compared with NCBI (National Center for Biotechnology Information) annotation. Corresponding protein-coding sequences (CDSs) were detected, but also CDSs that were exclusively determined by either NCBI or Bac Prot. A new Shine-Dalgarno sequence motif (50-AGCTGG-30) was extracted. Novel CDSs including PE-PGRS family protein genes and about 80 noncoding RNAs exhibiting high sequence conservation are presented. Previously found genetic differences between MAP-types are partially revised. Four of ten assumed MAP-S-specific large sequence polymorphism regions (LSPSs) are still present in MAP-C strains; new LSPSs were identified. Independently of the regional origin of the strains, the number of individual CDSs and single nucleotide variants confirms the strong similarity of MAP-C strains and shows higher diversity among MAP-S strains. This study givesambiguous results regarding the hypothesis that MAP-S is the evolutionary intermediate between MA Hand MAP-C, but it clearly shows a higher similarity of MAP to MAH than to Mycobacterium intracellulare.