The use of whole-genome analysis for identifying molecular markers of significant genetic clusters of Mycobacterium tuberculosis in Russia

Abstract

Tuberculosis is one of the re-emerging diseases that have epidemically spread in many regions worldwide. Understanding of the genetic basis for Mycobacterium tuberculosis adaptation to the human host is of a fundamental interest.
The aim of this study was to identify molecular markers for significant genetic clusters of M. tuberculosis in Russia based on a whole genome and bioinformatics analysis. Whole genome sequencing and phylogenetic analysis were performed for a representative sample of M. tuberculosis strains of the East Asian lineage (ancient and modern sublineages of the Beijing genotype) and the Euro-American lineage (strains of LAM, T and S genotypes). The phylogenetic analysis of genomic data (4500 polymorphic nucleotide positions) allowed to identify strain clusters and to determine their specific single nucleotide polymorphisms (SNPs). Specifically, an evolutionarily “young” cluster was identified within the LAM-RUS branch, including strains of the SIT252 and SIT266 spoligotypes. Modern (subtypes B0 and 94-32) and ancient sublineages were identified within
the Beijing genotype. Beijing and LAM cluster-specific SNPs were mainly found in gene categories “cell wall and cell processes” and “intermediary metabolism and respiration”. Variations in the genes of the “virulence” category were found only in strains of Beijing B0/W148, ancient Beijing and LAM-RUS (SIT252/266) groups. To conclude, phylogenetically neutral polymorphisms as well as mutations in virulence, adaptation, cell wall biosynthesis, respiration, and lipid metabolism genes were identified for emerging, potentially epidemic variants of the LAM and Beijing genotypes of M. tuberculosis.