Genomic Analysis of Multidrug-Resistant Mycobacterium tuberculosis Strains From Patients in Kazakhstan

Asset Daniyarov; Askhat Molkenov; Saule Rakhimova; Ainur Akhmetova; Dauren Yerezhepov; Lyailya Chingissova; Venera Bismilda; Bekzat Toksanbayeva; Anar Rakisheva; Ainur Akilzhanova; Ulan Kozhamkulov; Ulykbek Kairov

doi:10.3389/fgene.2021.683515

Genomic Analysis of Multidrug-Resistant Mycobacterium tuberculosis Strains From Patients in Kazakhstan

Front Genet. 2021 Nov 9:12:683515. doi: 10.3389/fgene.2021.683515. eCollection 2021.

Affiliations

¹ Laboratory of Bioinformatics and Systems Biology, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Nur-Sultan, Kazakhstan.
² Laboratory of Genomic and Personalized Medicine, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Nur-Sultan, Kazakhstan.
³ National Scientific Center of Phthisiopulmonology of the Republic of Kazakhstan, Almaty, Kazakhstan.
⁴ Department of Phthisiopulmonology, School of General Medicine, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan.

Abstract

Tuberculosis (TB) is an infectious disease that remains an essential public health problem in many countries. Despite decreasing numbers of new cases worldwide, the incidence of antibiotic-resistant forms (multidrug resistant and extensively drug-resistant) of TB is increasing. Next-generation sequencing technologies provide a high-throughput approach to identify known and novel potential genetic variants that are associated with drug resistance in Mycobacterium tuberculosis (Mtb). There are limited reports and data related to whole-genome characteristics of drug-resistant Mtb strains circulating in Kazakhstan. Here, we report whole-genome sequencing and analysis results of eight multidrug-resistant strains collected from TB patients in Kazakhstan. Genotyping and validation of all strains by MIRU-VNTR and spoligotyping methodologies revealed that these strains belong to the Beijing family. The spectrum of specific and potentially novel genomic variants (single-nucleotide polymorphisms, insertions, and deletions) related to drug resistance was identified and annotated. ResFinder, CARD, and CASTB antibiotic resistance databases were used for the characterization of genetic variants in genes associated with drug resistance. Our results provide reference data and genomic profiles of multidrug-resistant isolates for further comparative studies and investigations of genetic patterns in drug-resistant Mtb strains.

Keywords: MIRU-VNTR analysis; Mycobacterium tuberculosis; genetic variants; genomic analysis; multidrug resistant TB; spoligotyping; tuberculosis; whole genome.