AUTHOR=Zimpel Cristina Kraemer , Brandão Paulo E. , de Souza Filho Antônio F. , de Souza Robson F. , Ikuta Cássia Y. , Ferreira Neto José Soares , Camargo Naila C. Soler , Heinemann Marcos Bryan , Guimarães Ana M. S. 

TITLE=Complete Genome Sequencing of Mycobacterium bovis SP38 and Comparative Genomics of Mycobacterium bovis and M. tuberculosis Strains

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.02389

DOI=10.3389/fmicb.2017.02389

ISSN=1664-302X

ABSTRACT=<p><italic>Mycobacterium bovis</italic> causes bovine tuberculosis and is the main organism responsible for zoonotic tuberculosis in humans. We performed the sequencing, assembly and annotation of a Brazilian strain of <italic>M. bovis</italic> named SP38, and performed comparative genomics of <italic>M. bovis</italic> genomes deposited in GenBank. <italic>M. bovis</italic> SP38 has a traditional tuberculous mycobacterium genome of 4,347,648 bp, with 65.5% GC, and 4,216 genes. The majority of CDSs (2,805, 69.3%) have predictive function, while 1,206 (30.07%) are hypothetical. For comparative analysis, 31 <italic>M. bovis</italic>, 32 <italic>M. bovis</italic> BCG, and 23 <italic>Mycobacterium tuberculosis</italic> genomes available in GenBank were selected. <italic>M. bovis</italic> RDs (regions of difference) and Clonal Complexes (CC) were identified <italic>in silico</italic>. Genome dynamics of bacterial groups were analyzed by gene orthology and polymorphic sites identification. <italic>M. bovis</italic> polymorphic sites were used to construct a phylogenetic tree. Our RD analyses resulted in the exclusion of three genomes, mistakenly annotated as virulent <italic>M. bovis</italic>. <italic>M. bovis</italic> SP38 along with strain 35 represent the first report of CC European 2 in Brazil, whereas two other <italic>M. bovis</italic> strains failed to be classified within current CC. Results of <italic>M. bovis</italic> orthologous genes analysis suggest a process of genome remodeling through genomic decay and gene duplication. Quantification, pairwise comparisons and distribution analyses of polymorphic sites demonstrate greater genetic variability of <italic>M. tuberculosis</italic> when compared to <italic>M. bovis</italic> and <italic>M. bovis</italic> BCG (<italic>p</italic> ≤ 0.05), indicating that currently defined <italic>M. tuberculosis</italic> lineages are more genetically diverse than <italic>M. bovis</italic> CC and animal-adapted MTC (<italic>M. tuberculosis</italic> Complex) species. As expected, polymorphic sites annotation shows that <italic>M. bovis</italic> BCG are subjected to different evolutionary pressures when compared to virulent mycobacteria. Lastly, <italic>M. bovis</italic> phylogeny indicates that polymorphic sites may be used as markers of <italic>M. bovis</italic> lineages in association with CC. Our findings highlight the need to better understand host-pathogen co-evolution in genetically homogeneous and/or diverse host populations, considering the fact that <italic>M. bovis</italic> has a broader host range when compared to <italic>M. tuberculosis</italic>. Also, the identification of <italic>M. bovis</italic> genomes not classified within CC indicates that the diversity of <italic>M. bovis</italic> lineages may be larger than previously thought or that current classification should be reviewed.</p>