Genomic Characterization of Drug-Resistant Mycobacterium tuberculosis L2/Beijing Isolates from Astana, Kazakhstan

Auganova, Dana; Atavliyeva, Sabina; Amirgazin, Asylulan; Akisheva, Akmaral; Tsepke, Anna; Tarlykov, Pavel

doi:10.3390/antibiotics12101523

Cited by 6 publications

(1 citation statement)

References 60 publications

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“…In Kazakhstan, studies were carried out to investigate mutations in the M. tuberculosis genes responsible for drug resistance to various antibiotics [20,21]. Several studies were performed on the molecular genotyping [22,23] and whole-genome sequencing of M. tuberculosis [24][25][26]. However, Beijing genotype clusters and their association with mutations in drug-resistant genes have not been fully investigated.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of Beijing Central Asian/Russian Cluster 94-32 among Multidrug-Resistant M. tuberculosis in Kazakhstan

Akhmetova,

Bismilda,

Chingissova

et al. 2023

Antibiotics

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The Beijing genotype is the most distributed M. tuberculosis family in Kazakhstan. In this study, we identified dominant Beijing clusters in Kazakhstan and assessed their drug susceptibility profiles and association with the most widely spread mutation Ser531Leu of the rpoB gene and the mutation Ser315Thr of the katG gene associated with resistance to rifampicin and isoniazid, respectively. M. tuberculosis isolates (n = 540) from new TB cases were included in the study. MIRU-VNTR genotyping was performed for 540 clinical isolates to determine M. tuberculosis families using 24 loci. RD analysis was additionally performed for the Beijing isolates. The identification of mutations in the drug-resistance genes of M. tuberculosis was performed with allele-specific real-time PCR and Sanger sequencing. The Beijing genotype was identified in 60% (324/540) of the clinical isolates. Central Asian/Russian cluster 94-32 was the most distributed cluster among the Beijing isolates (50.3%; 163/324). Three other dominant Beijing clusters were identified as 94-33 (3.4%; 11/324), 100-32 (3.1%; 10/324) and 99-32 (3.1%; 10/324). The Beijing genotype was associated with drug-resistant TB (p < 0.0001), including multidrug-resistant TB (p < 0.0001), in our study. An association of the mutation Ser531Leu of the rpoB gene with the Beijing genotype was found (p < 0.0001; OR = 16.0000; 95%CI: 4.9161–52.0740). Among the Beijing isolates, cluster 94-32 showed an association with MDR-TB (p = 0.021). This is why the evaluation of the Beijing genotype and its clusters is needed to control MDR-TB in Kazakhstan.

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Section: Introductionmentioning

confidence: 99%

Prevalence of Beijing Central Asian/Russian Cluster 94-32 among Multidrug-Resistant M. tuberculosis in Kazakhstan

Akhmetova,

Bismilda,

Chingissova

et al. 2023

Antibiotics

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Clinical course of respiratory tuberculosis relapses in the Kazakh population depending on HLA-DRB1 gene alleles

Dilmagambetov,

Tanzharykova,

Sakhanova

et al. 2024

VirusDis.

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Large-scale statistical analysis of Mycobacterium tuberculosis genome sequences identifies compensatory mutations associated with multi-drug resistance

Billows,

Phelan,

Xia

et al. 2024

Sci Rep

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Tuberculosis (TB), caused by Mycobacterium tuberculosis, has a significant impact on global health worldwide. The development of multi-drug resistant strains that are resistant to the first-line drugs isoniazid and rifampicin threatens public health security. Rifampicin and isoniazid resistance are largely underpinned by mutations in rpoB and katG respectively and are associated with fitness costs. Compensatory mutations are considered to alleviate these fitness costs and have been observed in rpoC/rpoA (rifampicin) and oxyR’-ahpC (isoniazid). We developed a framework (CompMut-TB) to detect compensatory mutations from whole genome sequences from a large dataset comprised of 18,396 M. tuberculosis samples. We performed association analysis (Fisher’s exact tests) to identify pairs of mutations that are associated with drug-resistance, followed by mediation analysis to identify complementary or full mediators of drug-resistance. The analyses revealed several potential mutations in rpoC (N = 47), rpoA (N = 4), and oxyR’-ahpC (N = 7) that were considered either ‘highly likely’ or ‘likely’ to confer compensatory effects on drug-resistance, including mutations that have previously been reported and validated. Overall, we have developed the CompMut-TB framework which can assist with identifying compensatory mutations which is important for more precise genome-based profiling of drug-resistant TB strains and to further understanding of the evolutionary mechanisms that underpin drug-resistance.

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Genomic Characterization of Drug-Resistant Mycobacterium tuberculosis L2/Beijing Isolates from Astana, Kazakhstan

Cited by 6 publications

References 60 publications

Prevalence of Beijing Central Asian/Russian Cluster 94-32 among Multidrug-Resistant M. tuberculosis in Kazakhstan

Prevalence of Beijing Central Asian/Russian Cluster 94-32 among Multidrug-Resistant M. tuberculosis in Kazakhstan

Clinical course of respiratory tuberculosis relapses in the Kazakh population depending on HLA-DRB1 gene alleles

Large-scale statistical analysis of Mycobacterium tuberculosis genome sequences identifies compensatory mutations associated with multi-drug resistance

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