Genetic diversity of the Mycobacterium tuberculosis Beijing family based on IS6110, SNP, LSP and VNTR profiles from Thailand.

The Beijing family of Mycobacterium tuberculosis (MTB) has been shown to be highly virulent and is associated with tuberculosis outbreaks and drug resistance. To explore the evolutionary pathway of this genotype, 165 epidemiologically unlinked Beijing MTB isolates from Thailand were characterized based on IS6110, variable number of tandem repeats (VNTRs), region of differences (RDs) and single nucleotide polymorphisms (SNPs). Analysis based on VNTRs showed that 7 VNTRs were phylogenetically informative loci. Three of the seven VNTRs, 4156, 1982 and 1955, were promising markers for defining ancestral and modern Beijing sublineages. The evolutionary history of Beijing sublineages based on VNTR profiles showed dynamic changes in the repeat number, which also correlated with specific SNP STs. We constructed a refined, comprehensive phylogenetic tree based on multiple genetic markers from the Beijing strains from Thailand and combined the data with previous studies that were performed in South Africa and Japan. The phylogenetic tree showed how the modern Beijing and W-Beijing strains evolved from ancestral Beijing strains. The points at which the RD150 deletion occurred repeatedly were also demonstrated. The evolutionary scheme showed that most events were concordant with the SNP STs. Nevertheless, some SNPs used for sub-typing the Beijing family of MTB may not be irreversible, unique events.