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. 2019 Sep 30:12:3093-3102.
doi: 10.2147/IDR.S222943. eCollection 2019.

Resistance To First-Line Antituberculosis Drugs And Prevalence Of pncA Mutations In Clinical Isolates Of Mycobacterium tuberculosis From Zunyi, Guizhou Province Of China

Zhimin Cao  1 , Yuanbo Lan  1 , Ling Chen  1 , Min Xiang  1 , Zhiyuan Peng  1 , Jianyong Zhang  1 , Hong Zhang  1   2
Affiliations

Resistance To First-Line Antituberculosis Drugs And Prevalence Of pncA Mutations In Clinical Isolates Of Mycobacterium tuberculosis From Zunyi, Guizhou Province Of China

Zhimin Cao et al. Infect Drug Resist. .

Abstract

Background: China is one of the high-burden countries for multidrug-resistant tuberculosis (MDR-TB), and pyrazinamide is one of the anti-TB drugs used for the shorter MDR-TB treatment regimen. The aim of this study was to determine the correlation between pncA gene mutations and resistance to four first-line anti-TB drugs as well as treatment history in clinical isolates of Mycobacterium tuberculosis.

Patients and methods: M. tuberculosis clinical isolates were collected from 318 in-patients with smear-positive TB between October 2008 and September 2016 at a major hospital in Zunyi, Guizhou Province of China, and used for drug susceptibility testing against four first-line anti-TB drugs. Genomic DNA extracted from clinical isolates was used for PCR amplification and DNA sequencing of the pncA gene.

Results: Among 318 clinical isolates, 129 (40.6%), 170 (53.5%), 66 (20.8%) and 109 (34.3%) were resistant to rifampicin, isoniazid, ethambutol and streptomycin respectively. In addition, 124 clinical isolates were MDR-TB and 71.8% of them were previously treated cases. Sequencing results showed that 46.8% of MDR-TB and 2.2% of drug susceptible isolates harbored a pncA mutation, and 52 types of pncA mutations were detected from 64 isolates. The prevalence of pncA mutations in isolates resistant to first-line anti-TB drugs and previously treated TB cases was significantly higher than that in drug-susceptible isolates and new cases of TB.

Conclusion: High prevalence of pncA mutations in clinical isolates of M. tuberculosis from Zunyi, Guizhou Province of China, is correlated with resistance to four first-line anti-TB drugs, MDR-TB and previously treated TB cases.

Keywords: Mycobacterium tuberculosis; drug resistance; pncA mutation; pyrazinamide.

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Conflict of interest statement

HZ is employed by and has shares in Z-BioMed, Inc., which is involved in infectious disease research. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Distribution, mutant type and frequency of 64 pncA mutations detected in this study. Numbers are amino acid positions in the pncA coding region and numbers in brackets represent the number of isolates with the same mutation. Red symbol, MDR-TB; blue symbol, PDR-TB; and green symbol, Pan-S-TB.
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