Unusual Large-Scale Chromosomal Rearrangements in Mycobacterium tuberculosis Beijing B0/W148 Cluster Isolates

Abstract

The Mycobacterium tuberculosis (MTB) Beijing family isolates are geographically widespread, and there are examples of Beijing isolates that are hypervirulent and associated with drug resistance. One-fourth of Beijing genotype isolates found in Russia belong to the B0/W148 group. The aim of the present study was to investigate features of these endemic strains on a genomic level. Four Russian clinical isolates of this group were sequenced, and the data obtained was compared with published sequences of various MTB strain genomes, including genome of strain W-148 of the same B0/W148 group. The comparison of the W-148 and H37Rv genomes revealed two independent inversions of large segments of the chromosome. The same inversions were found in one of the studied strains after deep sequencing using both the fragment and mate-paired libraries. Additionally, inversions were confirmed by RFLP hybridization analysis. The discovered rearrangements were verified by PCR in all four newly sequenced strains in the study and in four additional strains of the same Beijing B0/W148 group. The other 32 MTB strains from different phylogenetic lineages were tested and revealed no inversions. We suggest that the initial largest inversion changed the orientation of the three megabase (Mb) segment of the chromosome, and the second one occurred in the previously inverted region and partly restored the orientation of the 2.1 Mb inner segment of the region. This is another remarkable example of genomic rearrangements in the MTB in addition to the recently published of large-scale duplications. The described cases suggest that large-scale genomic rearrangements in the currently circulating MTB isolates may occur more frequently than previously considered, and we hope that further studies will help to determine the exact mechanism of such events.

Proteomics for the Investigation of Mycobacteria

“…Types M2 and M11 are most widespread in Russia and comprise about 80% of all detected isolates [66, 67]. After exploring Beijing strains B0/W148 belonging to the M11 type, we confirmed their association with the development of multidrug resistance, found new potential ways of formation of anti-TB drug resistance, and described their unique genomic rearrangement [15]. …”

GenGraph: a python module for the simple generation and manipulation of genome graphs

“…First, the identification of large co-linear blocks, then the realignment of those blocks. This allowed for the creation of a genome graph containing multiple bacterial genomes, including the MTB isolate W-148 that contains large scale chromosomal rearrangements [9]. The created genome graph is thus able to capture all variants from large scale structural differences between isolates such as chromosomal rearrangements, down to smaller scale differences including SNPs and copy number variations.…”

A Nonsynonymous SNP Catalog of Mycobacterium tuberculosis Virulence Genes and Its Use for Detecting New Potentially Virulent Sublineages

“…2015). All of these factors lead to significant changes inside MT and the emergence of new lineages with higher drug resistance and virulence (Mokrousov 2013; Shitikov et al. 2014; Luo et al.…”