Prevalence and Molecular Characteristics Based on Whole Genome Sequencing of Mycobacterium tuberculosis Resistant to Four Anti-Tuberculosis Drugs from Southern Xinjiang, China

Aiketaguli Anwaierjiang; Quan Wang; Haican Liu; Chunjie Yin; Miao Xu; Machao Li; Mengwen Liu; Yan Liu; Xiuqin Zhao; Jinbao Liu; Guilian Li; Xiaokaiti Mijiti; Kanglin Wan

doi:10.2147/IDR.S320024

Prevalence and Molecular Characteristics Based on Whole Genome Sequencing of Mycobacterium tuberculosis Resistant to Four Anti-Tuberculosis Drugs from Southern Xinjiang, China

Infect Drug Resist. 2021 Aug 24:14:3379-3391. doi: 10.2147/IDR.S320024. eCollection 2021.

Authors

Affiliations

¹ College of Public Health, Xinjiang Medical University, Wulumuqi, 830011, People's Republic of China.
² The Eighth Affiliated Hospital of Xinjiang Medical University, Wulumuqi, 830001, People's Republic of China.
³ State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People's Republic of China.

^# Contributed equally.

Abstract

Objective: Drug-resistant tuberculosis is a major public health problem, especially in the southern region of Xinjiang, China; however, there is little information regarding drug resistance profiles and mechanism of Mycobacterium tuberculosis in this area. The aim of this study was to determine the prevalence and molecular characteristics of M. tuberculosis resistant to four anti-tuberculosis drugs from this area.

Methods: Three hundred and forty-six isolates from the southern region of Xinjiang, China were included and used to perform phenotypic drug susceptibility testing and whole genome sequencing (WGS). Mutations in seven loci associated with drug resistance, including rpoB for rifampicin (RMP), katG, inhA promoter and oxyR-ahpC for isoniazid (INH), rrs 530 and 912 loops and rpsL for streptomycin (STR), and embB for ethambutol (EMB), were characterized.

Results: Among 346 isolates, 106, 60, 70 and 29 were resistant to INH, RMP, STR and EMB, respectively; 132 were resistant to at least one of the four anti-tuberculosis drugs and 51 were multi-drug resistant (MDR). Beijing genotype and retreated patients showed a significantly increased risk for developing MDR tuberculosis. Compared with the phenotypic data, the sensitivity and specificity for WGS to predict resistance were 96.7% and 98.6% for RMP, 75.5% and 97.1% for INH, 68.6% and 99.6% for STR, 93.1% and 93.7% for EMB, respectively. The most common mutations conferring RMP, INH, STR and EMB resistance were Ser450Leu (51.7%) in rpoB, Ser315Thr (44.3%) in katG, Lys43Arg (35.7%) in rpsL and Met306Val (24.1%) in embB.

Conclusion: This study provides the first information on the prevalence and molecular characters of drug resistant M. tuberculosis in the southern region of Xinjiang, China, which will be helpful for choosing early detection methods for drug resistance (ig, molecular methods) and subsequently initiation of proper therapy of tuberculosis in this area.

Keywords: Mycobacterium tuberculosis; ethambutol; isoniazid; mutation; prevalence; resistance; rifampicin; streptomycin; whole-genome sequencing.

Grants and funding

This study was supported by the project (2017A03006-3) of the Major science and technology programs of Xinjiang Uygur Autonomous Region from department of Science and Technology, Xinjiang Uygur Autonomous Region and Mega Project of Research on the Prevention and Control of HIV/AIDS, Viral Hepatitis Infectious Diseases (2018ZX10103001-003-012) from the Ministry of Science and Technology, China. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.