Mycobacterium avium subspecies paratuberculosis (MAP) is the aetiological agent of Johne's disease (JD), a chronic enteritis that causes major losses to the global livestock industry. Further, it has been associated with human Crohn's disease. Several strains of MAP have been identified, the two major groups being sheep strain MAP, which includes the Type I and Type III sub-lineages, and the cattle strain or Type II MAP lineage, of which bison strains are a sub-grouping. Major genotypic, phenotypic and pathogenic variations have been identified in prior comparisons, but the research has predominately focused on cattle strains of MAP. In countries where the sheep industries are more prevalent, however, such as Australia and New Zealand, ovine JD is a substantial burden. An information gap exists regarding the genomic differences between sheep strain sub-lineages and the relevance of Type I and Type III MAP in terms of epidemiology and/or pathogenicity. We therefore investigated sheep MAP isolates from Australia and New Zealand using whole genome sequencing. For additional context, sheep MAP genome datasets were downloaded from the Sequence Read Archive and GenBank. The final dataset contained 18 Type III and 16 Type I isolates and the K10 cattle strain MAP reference genome. Using a pan-genome approach, an updated global phylogeny for sheep MAP from de novo assemblies was produced. When rooted with the K10 cattle reference strain, two distinct clades representing the lineages were apparent. The Australian and New Zealand isolates formed a distinct sub-clade within the type I lineage, while the European type I isolates formed another less closely related group. Within the type III lineage, isolates appeared more genetically diverse and were from a greater number of continents. Querying of the pan-genome and verification using BLAST analysis revealed lineage-specific variations (n = 13) including genes responsible for metabolism and stress responses. The genetic differences identified may represent important epidemiological and virulence traits specific to sheep MAP. This knowledge will potentially contribute to improved vaccine development and control measures for these strains.

鸟分枝杆菌 亚种 副结核病（MAP）是Johne病（JD）的病原体，该病是一种慢性肠炎，对全球畜牧业造成重大损失。此外，它与人类克罗恩氏病有关。已经确定了几种MAP菌株，其中两大类是绵羊MAP菌株，包括I型和III型亚谱系，以及牛或II型MAP谱系，其中野牛株是其中的一个亚组。在先前的比较中已经鉴定出主要的基因型，表型和致病性变异，但是该研究主要集中在MAP的牛品系上。然而，在绵羊产业比较普遍的国家，例如澳大利亚和新西兰，绵羊JD是一个沉重的负担。在流行病学和/或致病性方面，关于绵羊品系亚种之间的基因组差异以及I型和III型MAP的相关性存在信息鸿沟。因此，我们使用全基因组测序研究了来自澳大利亚和新西兰的绵羊MAP分离株。对于其他情况，可从Sequence Read Archive和GenBank下载绵羊MAP基因组数据集。最终数据集包含18种III型和16种I型分离株以及K10牛品系MAP参考基因组。使用全基因组方法，从 绵羊MAP基因组数据集可从Sequence Read Archive和GenBank下载。最终数据集包含18种III型和16种I型分离株以及K10牛品系MAP参考基因组。使用全基因组方法，从 绵羊MAP基因组数据集可从Sequence Read Archive和GenBank下载。最终数据集包含18种III型和16种I型分离株以及K10牛品系MAP参考基因组。使用全基因组方法，从从头程序集已生产。当以K10牛参考菌株为根时，两个明显的进化枝就代表了血统。澳大利亚和新西兰的分离株在I型谱系中形成了一个独特的亚分支，而欧洲的I型分离株则形成了另一个关系不太密切的群体。在III型谱系中，分离株的遗传多样性更高，并且来自更多的大陆。泛基因组的查询和使用BLAST分析的验证揭示了谱系特异性变异（ñ= 13）包括负责代谢和应激反应的基因。鉴定出的遗传差异可能代表了绵羊MAP特有的重要流行病学和毒力特征。这些知识可能会有助于改善这些菌株的疫苗开发和控制措施。