AUTHOR=Hsu Chung-Yi , Wu Chia-wei , Talaat Adel M.

TITLE=Genome-Wide Sequence Variation among Mycobacterium avium Subspecies paratuberculosis Isolates: A Better Understanding of Johne’s Disease Transmission Dynamics

JOURNAL=Frontiers in Microbiology

VOLUME=2

YEAR=2011

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2011.00236

DOI=10.3389/fmicb.2011.00236

ISSN=1664-302X

ABSTRACT=<p><italic>Mycobacterium avium</italic> subspecies <italic>paratuberculosis</italic> (<italic>M. ap</italic>), the causative agent of Johne’s disease, infects many farmed ruminants, wild-life animals, and recently isolated from humans. To better understand the molecular pathogenesis of these infections, we analyzed the whole-genome sequences of several <italic>M. ap</italic> and <italic>M. avium</italic> subspecies <italic>avium</italic> (<italic>M. avium</italic>) isolates to gain insights into genomic diversity associated with variable hosts and environments. Using Next-generation sequencing technology, all six <italic>M. ap</italic> isolates showed a high percentage of similarity (98%) to the reference genome sequence of <italic>M. ap</italic> K-10 isolated from cattle. However, two <italic>M. avium</italic> isolates (DT 78 and Env 77) showed significant sequence diversity (only 87 and 40% similarity, respectively) compared to the reference strain <italic>M. avium</italic> 104, a reflection of the wide environmental niches of this group of mycobacteria. Within the <italic>M. ap</italic> isolates, genomic rearrangements (insertions/deletions) were not detected, and only unique single nucleotide polymorphisms (SNPs) were observed among <italic>M. ap</italic> isolates. While more of the SNPs (~100) in <italic>M. ap</italic> genomes were non-synonymous, a total of ~6,000 SNPs were detected among <italic>M. avium</italic> genomes, most of them were synonymous suggesting a differential selective pressure between <italic>M. ap</italic> and <italic>M. avium</italic> isolates. In addition, SNPs-based phylo-genomics had a enough discriminatory power to differentiate between isolates from different hosts but yet suggesting a bovine source of infection to other animals examined in this study. Interestingly, the human isolate (<italic>M. ap</italic> 4B) was closely related to a <italic>M. ap</italic> isolate from a dairy facility, suggesting a common source of infection. Overall, the identified phylo-genomes further supported the idea of a common ancestor to both <italic>M. ap</italic> and <italic>M. avium</italic> isolates. Genome-wide analysis described here could provide a strong foundation for a population genetic structure that could be useful for the analysis of mycobacterial evolution and for the tracking of Johne’s disease transmission among animals.</p>