Mosaic Structure as the Main Feature of Mycobacterium bovis BCG Genomes

Abstract

Background: The genome stability of attenuated live BCG vaccine preventing the acute forms of childhood tuberculosis is an important aspect of vaccine production. The purpose of our study was a whole genome comparative analysis of BCG sub-strains and identification of potential triggers of sub-strains' transition. Results: Genomes of three BCG Russia seed lots (1963, 1982, 2006 years) have been sequenced, and the stability of vaccine sub-strain genomes has been confirmed. A comparative genome analysis of nine Mycobacterium bovis BCG and three M. bovis strains revealed their specific genome features associated with prophage profiles. A number of prophage-coded homologs to Caudovirales ORFs were common to all BCG genomes. Prophage profiles of BCG Tice and BCG Montreal genomes were unique and coded homologs to herpes viruses ORFs. The data of phylogenetic analysis of BCG sub-strain groups based on whole genome sequences and genome restriction maps were in congruence with prophage profiles. The only fragmentary similarity of specific prophage sequences of BCG Tice, BCG Montreal, and BCG Russia 368 in pair-wise alignments was observed, suggesting the impact of prophages on mosaic structure of genomes. Conclusions: The whole genome sequencing approach is essential for genomes with mosaic structure, harboring numerous prophage sequences. Tools for prophage search are effective instruments in this analysis.

Transcriptional Profiling of Homologous Recombination Pathway Genes in Mycobacterium bovis BCG Moreau

“…But, other studies do not identify this mutation and observe a HR-efficient phenotype, like that of BCG Pasteur (and as we found in our UV exposure assays). Some authors correlate this discrepancy with BCG Russia not being clonal, but rather considered as a population of related bacteria [43].…”

“…It is long known that some mycobacteria, especially those that are important human and animal pathogens, are very genomically stable regarding lateral gene transfer, and this is due to several reasons, such as low growth rate and cell wall structure, among others [43]. This contrasts with other human pathogens that are able to acquire plasmids, genetic mobile elements, and DNA fragments from the environment carrying pathogenicity, virulence, and antibiotic-resistance genes, which can improve bacterial fitness [49,50].…”