Abstract
Mycobacterium tuberculosis Beijing genotype originated in China and has undergone a dramatic population growth and global spread in the last century. Here, a collection of M. tuberculosis Beijing family isolates from different provinces across all China was genotyped by high-resolution (24-MIRU-VNTR) and low-resolution, high-rank (modern and ancient sublineages) markers. The molecular profiles and global and local phylogenies were compared to the strain phenotype and patient data. The phylogeographic patterns observed in the studied collection demonstrate that large-scale (but not middle/small-scale) distance remains one of the decisive factors of the genetic divergence of M. tuberculosis populations. Analysis of diversity and network topology of the local collections appears to corroborate a recent intriguing hypothesis about Beijing genotype originating in South China. Placing our results within the Eurasian context suggested that important Russian B0/W148 and Asian/Russian A0/94-32 epidemic clones of the Beijing genotype could trace their origins to the northeastern and northwestern regions of China, respectively. The higher clustering of the modern isolates in children and lack of increased MDR rate in any sublineage suggest that not association with drug resistance but other (e.g., speculatively, virulence-related) properties underlie an enhanced dissemination of the evolutionarily recent, modern sublineage of the Beijing genotype in China.
Highlights
M. tuberculosis is a clonal species and its different lineages are marked with clearly different “curricula vitae”, some having declined even in the areas of their origin (M. africanum in West Africa being the most remarkable example), others having undergone a dramatic increase in effective population size and global dispersal
In addition to large sublineages, clonal clusters within the Beijing genotype have been identified by high-resolution genotyping (IS6110-RFLP and/or 24-VNTR typing)
The former is termed as Russian/Asian clone CC1 defined by 24-MIRU-VNTR clustering[3] and corresponds to the IS6110-RFLP-defined A0-cluster[16,17]
Summary
M. tuberculosis is a clonal species and its different lineages are marked with clearly different “curricula vitae”, some having declined even in the areas of their origin (M. africanum in West Africa being the most remarkable example), others having undergone a dramatic increase in effective population size and global dispersal. In addition to large sublineages, clonal clusters within the Beijing genotype have been identified by high-resolution genotyping (IS6110-RFLP and/or 24-VNTR typing) These include strain W that caused the MDR-TB outbreak in New York city in the mid-1990s14, Gran Canaria Beijing strain GC1237 whose transmission is ongoing[15], and two large clonal clusters circulating in the countries of the former USSR and named 94–32 and B0/W148. The former is termed as Russian/Asian clone CC1 defined by 24-MIRU-VNTR clustering[3] and corresponds to the IS6110-RFLP-defined A0-cluster[16,17]. Due to difficulty to isolate strains from children, such studies are rare
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