SNP/RD Typing of Mycobacterium tuberculosis Beijing Strains Reveals Local and Worldwide Disseminated Clonal Complexes

Abstract

The Beijing strain is one of the most successful genotypes of Mycobacterium tuberculosis worldwide and appears to be highly homogenous according to existing genotyping methods. To type Beijing strains reliably we developed a robust typing scheme using single nucleotide polymorphisms (SNPs) and regions of difference (RDs) derived from whole-genome sequencing data of eight Beijing strains. SNP/RD typing of 259 M. tuberculosis isolates originating from 45 countries worldwide discriminated 27 clonal complexes within the Beijing genotype family. A total of 16 Beijing clonal complexes contained more than one isolate of known origin, of which two clonal complexes were strongly associated with South African origin. The remaining 14 clonal complexes encompassed isolates from different countries. Even highly resolved clonal complexes comprised isolates from distinct geographical sites. Our results suggest that Beijing strains spread globally on multiple occasions and that the tuberculosis epidemic caused by the Beijing genotype is at least partially driven by modern migration patterns. The SNPs and RDs presented in this study will facilitate future molecular epidemiological and phylogenetic studies on Beijing strains.

Disclosure of Selective Advantages in the “modern” Sublineage of the Mycobacterium tuberculosis Beijing Genotype Family by Quantitative Proteomics

“…Selection of a Heterogeneous Set of M. tuberculosis Beijing Genotype Strains-To cover the full spectrum of the genotype family, we selected 14 ancient and 14 modern Beijing strains from a previous selection of 259 M. tuberculosis strains (40). Furthermore, we included the successful modern Beijing strain B0/W148, that comprises one-fourth of the M. tuberculosis Beijing isolates in different parts of Russia (41)(42)(43).…”

“…Molecular Typing Methods-M. tuberculosis Beijing strains were selected from a previously published selection of 259 Beijing strains (40). Fourteen ancient and 14 modern Beijing strains were included in the study to optimally represent the M. tuberculosis family.…”

“…Therefore, 14 ancient Beijing and 15 modern Beijing strains were selected from a published collection of 259 Beijing strains (40). The selected strains were representative of 13 countries on four continents i.e.…”

Analysis of Mutations in Streptomycin-Resistant Strains Reveals a Simple and Reliable Genetic Marker for Identification of the Mycobacterium tuberculosis Beijing Genotype

“…The isolates of the Beijing family of M. tuberculosis are characterized by their increased ability to spread and cause disease and their increased association with drug resistance in comparison with the levels for non-Beijing strains (2). Because of this, many methods have been developed that are aimed at identifying and differentiating M. tuberculosis Beijing isolates (3)(4)(5)(6). There are several methods for identifying Beijing isolates, including spoligotyping, restriction fragment length polymorphism (RFLP) using IS6110 as a probe, or the presence of a copy of IS6110 in the dnaA region (7).…”

Epidemiological investigation of Pseudomonas aeruginosa isolates from a six-year-long hospital outbreak using high-throughput whole genome sequencing

“…Several recent studies have shown that analysis of single nucleotide polymorphisms (SNPs) in bacterial genomes provides a means of determining relatedness between epidemiologically linked isolates and tracking bacterial evolution over periods of months to years [12][13][14][15][16]. In particular, several studies have tracked the genetic changes that emerge during long-term colonisation of cystic fibrosis patients [17,18].…”