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

Author:

Akhmetova Ainur12,Bismilda Venera3ORCID,Chingissova Lyailya3,Filipenko Maxim45ORCID,Akilzhanova Ainur1ORCID,Kozhamkulov Ulan1

Affiliation:

1. Laboratory of Genomic and Personalized Medicine, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana 010000, Kazakhstan

2. Department of General Biology and Genomics, L.N. Gumilyov Eurasian National University, Astana 010000, Kazakhstan

3. National Scientific Center of Phthisiopulmonology of the Republic of Kazakhstan, Almaty 050000, Kazakhstan

4. Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Novosibirsk 630000, Russia

5. Faculty of Natural Sciences, Novosibirsk State University, Novosibirsk 630090, Russia

Abstract

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.

Funder

Ministry of Education and Science of the Republic of Kazakhstan

Nazarbayev University

Publisher

MDPI AG

Subject

Pharmacology (medical),Infectious Diseases,Microbiology (medical),General Pharmacology, Toxicology and Pharmaceutics,Biochemistry,Microbiology

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