Comparative Genotyping of Human and Bovine-Derived MAP Isolates
An argument previously raised against the potential link between MAP and Crohn's disease was the perception that the genotypes of human-derived MAP isolates are significantly different from those of bovine origin (Sartor, 2005).
This argument originated from research using multiplex PCR of IS900 integration loci (MPIL) fingerprinting, which found that bovine isolates clustered together, whereas human and ovine isolates were more diverse (Motiwala et al., 2003). Many research studies followed reporting similarity between MAP cattle and human isolates, using several different comparative genomics methods: DNA microarrays, IS 1311 PCR restriction enzyme analysis, short-sequence repeat genotyping and, most recently, whole genome sequencing (Paustian et al., 2008; Singh et al., 2009; Wynne et al., 2011; Bannantine et al., 2014; Timms et al., 2015). The latter, most definitive method, has repeatedly shown that human MAP isolates are similar to bovine isolates, in different countries. Bannantine et al. (2014) reported the whole genome sequence of MAP isolated from the breast milk of a person with Crohn's disease and determined the isolate was highly similar to those of bovine origin. Another study that sequenced the genome of a human MAP isolate 43,545 also found that it was most closely related to bovine type (Timms et al., 2015). Wynne et al. (2011) performed comparative genomics on seven human MAP isolates (four from Crohn's disease patients), two bovine isolates and one ovine isolate. Sequencing again revealed that all human-derived isolates were similar to one another and closely related to a bovine isolate.When considering the presented evidence, it can be concluded that most human MAP isolates studied have the genotype of bovine MAP. While some variation has been described between human isolates (Wynne et al., 2014), it is noted that single nucleotide polymorphism (SNP) genotyping of MAP isolates from 26 dairy herds has revealed heterogeneity, both within and between herds (Amin et al., 2015). Unless MAP is proposed to have ‘jumped' once into humans, and that clone subsequently spread uniquely in humans, there is little reason to anticipate that there should be a human-specific genotype. Additionally, if a MAP lineage associated with sheep was isolated from a human sample, this would not invalidate the zoonotic potential of MAP; rather it would point to a different potential source.
3.6
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