Comparative genomics and genomic epidemiology of mycobacterium avium subsp. paratuberculosis strains

Two phenotypically distinct strains of Mycobacterium avium subsp. paratuberculosis (MAP) were recognized in the 1930s but it was not until the introduction of restriction endonuclease analysis (REA) in the mid-1980s that these two strains, MAP-C and MAP-S, could be distinguished genetically. Since then, a plethora of molecular typing techniques has been applied to MAP isolates (reviewed by Li et al. 2016; Fawzy et al., 2018) and a complex nomenclature for MAP strains has evolved. Currently, the most widely used genotyping method is Mycobacterial Interspersed Repetitive Units – Variable-Number Tandem Repeats (MIRU-VNTR). However, it has limited discriminatory power within the major lineages and does not always accurately reflect genetic relatedness since the repeat sequences are subject to homoplasy (Ahlstrom et al., 2015; Bryant et al., 2016). Whole genome sequencing (WGS) supplies the ultimate resolution and has revolutionized MAP research. It has enabled determination of single nucleotide polymorphism (SNP) level diversity, clarified phylogenetic relationships between divergent lineages and closely related strains and spawned the development of novel genotyping methods based on informative canonical SNPs (Leão et al. 2016; Ahlstrom et al. 2016b). This chapter presents an overview of comparative genomics and epidemiology of MAP strains and also highlights the role that WGS has played in increasing our understanding of MAP strain diversity.