Evaluation of the frequency of mutation genes in multidrug-resistant tuberculosis (MDR-TB) strains in Beijing, China

Y Liu,Z Zhang,Y Sun,Q Xing,C Yao,J Yu,W Ren,S Wang,C Li,B Ding,X Zhang

doi:10.1017/s0950268820003131

Abstract

The aim of this study was to explore the frequency and distribution of gene mutations that are related to isoniazid (INH) and rifampin (RIF)-resistance in the strains of the multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M.tb) in Beijing, China. In this retrospective study, the genotypes of 173 MDR-TB strains were analysed by spoligotyping. The katG, inhA genes and the promoter region of inhA, in which genetic mutations confer INH resistance; and the rpoB gene, in which genetic mutations confer RIF resistance, were sequenced. The percentage of resistance-associated nucleotide alterations among the strains of different genotypes was also analysed. In total, 90.8% (157/173) of the MDR strains belonged to the Beijing genotype. Population characteristics were not significantly different among the strains of different genotypes. In total, 50.3% (87/173) strains had mutations at codon S315T of katG; 16.8% (29/173) of strains had mutations in the inhA promoter region; of them, 5.5% (15/173) had point mutations at -15 base (C→T) of the inhA promoter region. In total, 86.7% (150/173) strains had mutations at rpoB gene; of them, 40% (69/173) strains had mutations at codon S531L of rpoB. The frequency of mutations was not significantly higher in Beijing genotypic MDR strains than in non-Beijing genotypes. Beijing genotypic MDR-TB strains were spreading in Beijing and present a major challenge to TB control in this region. A high prevalence of katG Ser315Thr, inhA promoter region (-15C→T) and rpoB (S531L) mutations was observed. Molecular diagnostics based on gene mutations was a useful method for rapid detection of MDR-TB in Beijing, China.

Highlights

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) complex infection, is a major threat to public health around the world
3881 (84.7%) strains were from patients who had been cured, and of these, 176 (3.8%) strains were from multidrug-resistant tuberculosis (MDR-TB) patients
Genotyping of the strains indicated that the Beijing genotype accounted for 90.8% (157/173) of the MDR-TB strains

Summary

Introduction

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) complex infection, is a major threat to public health around the world. MDR-TB is defined as TB that is caused by M.tb resistant to at least the two most powerful anti-TB drugs, isoniazid (INH) and rifampin (RIF) [2]. It has been well established that most INH-resistant strains possess mutations in katG and/or the promoter region of inhA [4,5,6]. M.tb strains resistant to INH usually carry mutations in katG gene and in the promoter of inhA [7, 8]. INH resistance is most commonly caused by the substitution of a single nucleotide at codon 315 in katG [9, 10]. Resistance to RIF in M.tb strains arises primarily from mutations in the rpoB gene [3, 11, 12]. The most common mutations in the RRDR region occur at codons 513, 516, 526 and 531

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