Genome
From an epidemiological perspective, whole genome sequencing (WGS) provides the greatest resolution of strain differences in MAP. With the availability of benchtop nextgeneration sequencing platforms, it is now possible to quickly track within-herd and between-herd transmissions at higher resolutions than achieved using short sequence repeat (SSR) (Amonsin et al., 2004) or variable number tandem repeats (VNTR) typing methods (Castellanos et al., 2010; Douarre et al., 2011).
This approach has been demonstrated to be effective for defining the role of wildlife for Mycobacterium bovis transmission in New Zealand (Price-Carter et al., 2018) and the USA (Salvador et al., 2019). Although MAP WGS of strains has lagged well behind its M. bovis counterpart, there are now additional MAP genome sequences isolated from divergent hosts to serve as a foundation for comparisons.The first genome sequence of MAP has been available for about 15 years (Li etal., 2005). This bovine isolate, termed K-10 for the 10th bacterial colony cultured from a Holstein cow on a Wisconsin dairy farm, is 4.8 Mb in length and 69% GC content. More genomes of MAP have since followed including additional bovine isolates (Amin et al., 2015; Mobius et al., 2017), ovine MAP-S strains in the USA and Australia (Bannantine etal., 2012; Brauning etal., 2019), camel MAP-S strains (Ghosh et al., 2012) and human MAP-C strains (Wynne et al., 2011; Bannantine et al., 2014). Most of the genetic diversity resides in insertions/deletions termed large sequence polymorphisms or LSPs (Semret et al., 2005). These regions vary from 5 kb to >100 kb. Another source of diversity appears in single nucleotide polymorphisms (SNPs), which have been catalogued in detail using the aforementioned SSR and VNTR assays. Interestingly, MAP lacks a genomic region identified in Mycobacterium avium 109 as a pathogenicity island important for macrophage and amoeba infection (Danelishvili et al., 2007).
7.4