Genomic characterization of MDR/XDR-TB in Kazakhstan by a combination of high-throughput methods predominantly shows the ongoing transmission of L2/Beijing 94–32 central Asian/Russian clusters

Abstract

Background Kazakhstan remains a high-burden TB prevalence country with a concomitent high-burden of multi-drug resistant tuberculosis. For this reason, we performed an in depth genetic diversity and population structure characterization of Mycobacterium tuberculosis complex (MTC) genetic diversity in Kazakhstan with both patient and community benefit. Methods A convenience sample of 700 MTC DNA cultures extracts from 630 tuberculosis patients recruited from 12 out of 14 regions in Kazakhstan, between 2010 and 2015, was independently studied by high-throughput hybridization-based methods, TB-SPRINT (59-Plex, n = 700), TB-SNPID (50-Plex, n = 543). DNA from 391 clinical isolates was successfully typed by two methods. To resolve the population structure of drug-resistant clades in more detail two complementary assays were run on the L2 isolates: an IS 6110 -NTF insertion site typing assay and a SigE SNP polymorphism assay. Results Strains belonged to L2/Beijing and L4/Euro-American sublineages; L2/Beijing prevalence totaled almost 80%. 50% of all samples were resistant to RIF and to INH., Subtyping showed that: (1) all L2/Beijing were “modern” Beijing and (2) most of these belonged to the previously described 94–32 sublineage (Central Asian/Russian), (3) at least two populations of the Central Asian/Russian sublineages are circulating in Kazakhstan, with different evolutionary dynamics. Conclusions For the first time, the global genetic diversity and population structure of M. tuberculosis genotypes circulating in Kazakhstan was obtained and compared to previous local studies. Results suggest a region-specific spread of a very limited number of L2/Beijing clonal complexes in Kazakhstan many strongly associated with an MDR phenotype. Electronic supplementary material The online version of this article (10.1186/s12879-019-4201-2) contains supplementary material, which is available to authorized users.

Connection between two historical tuberculosis outbreak sites in Japan, Honshu, by a new ancestral Mycobacterium tuberculosis L2 sublineage

“…Although L2 origin is suspected to be in China and L2 is predominant in east Asia, its exact place and time of emergence are still highly debated [ 8 – 10 ]. L2 clinical isolates have developed specific virulence and drug-resistance features that contribute to their epidemic success [ 6 , 11 – 13 ]. From an evolutionary standpoint, L2 has developed a high IS 6110 copy number lifestyle, that could have fostered a hypermutator phenotype that may have increased the virulence or fitness of some of these isolates [ 14 , 15 ].…”

“…L2 clinical isolates have developed specific virulence and drug-resistance features that contribute to their epidemic . https://doi.org/10.1017/S0950268822000048 success [6,[11][12][13]. From an evolutionary standpoint, L2 has developed a high IS6110 copy number lifestyle, that could have fostered an hypermutator phenotype that may have increased the virulence or fitness of some of these isolates [14,15].…”

Connection between two historical tuberculosis outbreak sites in Japan, Honshu, due to a new ancestral L2 sublineage

“…L2 finds its origin in China and is predominant in Asia [7,8]. The adaptation ability of these bacilli to develop specific pathogenic features including compensatory mutations in genes that restore their fitness have largely contributed to their epidemic success and to the global spreading of multidrug resistant strains [6,[9][10][11].…”

Genomic analysis of Latin American-Mediterranean family of Mycobacterium tuberculosis clinical strains from Kazakhstan

“…(8,11) In previous studies, the LAM genetic family was found at a proportion of 11% in a sample of 470 M. tuberculosis isolates from 12 provinces of Kazakhstan (51/470 = 10.85%). (6,12) The other study describes local LAM isolates represented mainly by RD115 LAM-RUS sublineage (29/30 = 96.67%). (13) Additionally, recent findings observed a very first isolate with an RD-Rio deletion (LAM RD-Rio) not endemic to Central Asia.…”

“… 5 To date, LAM is the most predominant family of M. tuberculosis observed in Kazakhstan after the Beijing family. 6 Region of difference (RD) loci divided the LAM lineage into several sublineages, namely RD-Rio, RD174, and RD115. RD-Rio sublineage is defined by 26 kb deletion and generally concomitant with large deletion RD174.…”