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Characterization of novel Mycobacterium tuberculosis pncA gene mutations in clinical isolates from the Ukraine.

Abstract：

:Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis cases in the Ukraine are increasing. Pyrazinamide (PZA) is critically important for first- and second-line tuberculosis (TB) treatment regimes. However, PZA drug susceptibility testing is time consuming and technically challenging. The present study utilized Next-generation sequencing (NGS) to identify mutations in the pncA gene from clinical isolates and to assess the prevalence of pncA gene mutations in MDR/XDR-TB patients. Clinical isolates were inactivated in molecular transport media and shipped from Kharkiv, Ukraine, to San Antonio, TX. Whole-genome and targeted pncA gene sequencing was carried out using Illumina MiSeq instrumentation. Mutations were noted in 67 of 91 (74%) clinical isolates comprising substitutions, insertions, and deletions in the pncA coding and upstream promoter region. Of 45 mutation types, there were 11 novel, i.e., to date unknown, pncA mutations identified of which 3 were confirmed PZA resistant. Seven isolates contained mixed base mutations, whereas 4 harbored doubled mutations. Data reported here further support use of NGS for pncA gene characterization and may contribute in significant fashion to PZA therapy, especially in MDR- and XDR-TB patients.

journal_name

Diagn Microbiol Infect Dis

journal_title

Diagnostic microbiology and infectious disease

authors

Daum LT,Konstantynovska OS,Solodiankin OS,Poteiko PI,Bolotin VI,Rodriguez JD,Gerilovych AP,Chambers JP,Fischer GW

doi

10.1016/j.diagmicrobio.2018.10.018

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

334-338

issue

4

eissn

0732-8893

issn

1879-0070

pii

S0732-8893(18)30585-6

journal_volume

93

pub_type

杂志文章

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