Abstract

The human-adapted strains of the Mycobacterium tuberculosis complex (MTBC) comprise seven phylogenetic lineages originally associated with their geographical distribution. Here, we report the genomes of three drug-resistant clinical isolates of the Latin American-Mediterranean (LAM) family collected in Kazakhstan. We utilised whole-genome sequencing to study the distribution and drug resistance of these isolates. Phylogenetic analysis grouped the genomes described in this study with the sequences from Russia, Uzbekistan, and Kazakhstan belonging to the LAM family. One isolate has acquired extensive drug resistance to seven antituberculosis drugs. Our results suggest at least two multi-drug resistant (MDR)/extensively drug-resistant (XDR)-associated genotypes of the LAM family circulate in Kazakhstan.

Highlights

  • Mycobacterium tuberculosis is a human pathogen with diverging lineages initially associated with a specific geographic region.[1]

  • In 2014, the Latin American-Mediterranean (LAM) family has already been observed in 47 countries with different prevalence rates, including several Central Asian countries (Kazakhstan, Uzbekistan, and Turkmenistan) and neighboring Russia.[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.(7) The other sublineage is characterised by deletion RD115, which includes the LAM-RUS branch with a specific insertion of IS6110 into the plcA gene.[8]

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Summary

SHORT COMMUNICATION

The human-adapted strains of the Mycobacterium tuberculosis complex (MTBC) comprise seven phylogenetic lineages originally associated with their geographical distribution. We report the genomes of three drug-resistant clinical isolates of the Latin American-Mediterranean (LAM) family collected in Kazakhstan. Very few local collections of MTBC isolates were tested for RD loci or IS6110 insertions.[13] there are only three whole-genome sequences (WGS) of the LAM isolates from Kazakhstan published to date.[5] The additional genomes will provide more data on the genetic variations occurring in drug-resistant LAM family isolates circulating in Kazakhstan and neighboring countries. Prevalence of the LAM-RUS isolates in local samples is especially intriguing since Lineage 4 is the most heterogeneous lineage of M. tuberculosis, consisting of 10 different sublineages, determined by the absence of specific RD loci called RD115, RD122, RD174, RD182, RD183, RD193, RD219, RD724, RD726, and RD761.(36) All three WGS genomes of the local LAM isolates sequenced by Stucki et al[5] were defined by the large deletion RD115 (Table III).

SRA accession Genome size GC content Coverage
Drug resistance
Findings
This study
Full Text
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