Abstract
Background Mycobacterium tuberculosis has a global population structure consisting of six main phylogenetic lineages associated with specific geographic regions and human populations. One particular M. tuberculosis genotype known as “Beijing” has repeatedly been associated with drug resistance and has been emerging in some parts of the world. “Beijing” strains are traditionally defined based on a characteristic spoligotyping pattern. We used three alternative genotyping techniques to revisit the phylogenetic classification of M. tuberculosis complex (MTBC) strains exhibiting the typical “Beijing” spoligotyping pattern.Methods and FindingsMTBC strains were obtained from an ongoing molecular epidemiological study in Switzerland and Nepal. MTBC genotyping was performed based on SNPs, genomic deletions, and 24-loci MIRU-VNTR. We identified three MTBC strains from patients originating from Tibet, Portugal and Nepal which exhibited a spoligotyping patterns identical to the classical Beijing signature. However, based on three alternative molecular markers, these strains were assigned to Lineage 3 (also known as Delhi/CAS) rather than to Lineage 2 (also known as East-Asian lineage). Sequencing of the RD207 in one of these strains showed that the deletion responsible for this “Pseudo-Beijing” spoligotype was about 1,000 base pairs smaller than the usual deletion of RD207 in classical “Beijing” strains, which is consistent with an evolutionarily independent deletion event in the direct repeat (DR) region of MTBC.ConclusionsWe provide an example of convergent evolution in the DR locus of MTBC, and highlight the limitation of using spoligotypes for strain classification. Our results indicate that a proportion of “Beijing” strains may have been misclassified in the past. Markers that are more phylogenetically robust should be used when exploring strain-specific differences in experimental or clinical phenotypes.
Highlights
We provide an example of convergent evolution in the direct repeat (DR) locus of M. tuberculosis complex (MTBC), and highlight the limitation of using spoligotypes for strain classification
Mycobacterium tuberculosis complex (MTBC) adapted to humans consist of six main phylogeographical lineages [1]
We recently identified novel single nucleotide polymorphism (SNP) markers that define the main phylogenetic lineages [8,12]
Summary
Mycobacterium tuberculosis complex (MTBC) adapted to humans consist of six main phylogeographical lineages [1]. One particular MTBC genotype known as ‘‘Beijing’’ has repeatedly been associated with drug resistance [4] and increased virulence in animal models [2]. This genotype was first described in 1995 [5], and has traditionally been defined based on a characteristic spoligotyping pattern [6]. Phylogenetic analyses showed that the Beijing strain family belongs to Lineage 2 (known as East Asian lineage), which is one of the six main human-adapted lineages of MTBC [7,8]. We used three alternative genotyping techniques to revisit the phylogenetic classification of M. tuberculosis complex (MTBC) strains exhibiting the typical ‘‘Beijing’’ spoligotyping pattern
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