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Tuberculosis (Edinb). 2015 Sep;95(5):608-12. doi: 10.1016/j.tube.2015.05.013. Epub 2015 Jun 2.

Resistance to pyrazinamide in Russian Mycobacterium tuberculosis isolates: pncA sequencing versus Bactec MGIT 960.

Author information

1
Laboratory of Bacterial Genetics, Department of Genetics and Biotechnology, Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkina Str., 119991 Moscow, Russia.
2
Department of Microbiology, Central TB Research Institute, Russian Academy of Medical Sciences, 2 Yauzskaya Alleya, 107564 Moscow, Russia.
3
W. Harry Feinstone Department of Molecular Microbiology & Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD 21205, USA.
4
Laboratory of Bacterial Genetics, Department of Genetics and Biotechnology, Vavilov Institute of General Genetics, Russian Academy of Sciences, 3 Gubkina Str., 119991 Moscow, Russia. Electronic address: valerid@vigg.ru.

Abstract

Resistance to pyrazinamide (PZA) may impact clinical outcome of anti-tuberculosis chemotherapy. PZA susceptibility testing using MGIT 960 is not reliable and little information is available on the prevalence of PZA resistance in Russia. A collection of 64 clinical isolates of Mycobacterium tuberculosis, including 35 multidrug resistant and extensively drug-resistant (MDR/XDR), was analyzed for PZA resistance using MGIT 960, Wayne test, and sequencing of PZA resistance genes pncA, rpsA and panD. In addition, we analyzed 519 MDR-TB strains for susceptibility to PZA by MGIT 960. Sequencing of pncA revealed 17 of 25 (68%) MDR strains and all 10 XDR strains harboring pncA mutations. A correlation of φ = 0.81 between MGIT 960 and pncA sequencing was observed. Mutations in rpsA and panD not associated with PZA resistance as defined by MGIT 960 were identified. We found 1 PZA-resistant strain without mutations in known PZA resistance genes. Almost 73% of MDR-TB strains isolated in Moscow, Russia, were PZA-resistant by MGIT 960 testing of 519 MDR-TB clinical isolates. Further studies are needed to determine the role of rpsA and panD mutations in possible low-level PZA resistance and to identify the molecular basis of new PZA resistance in the isolate without known PZA resistance mutations.

KEYWORDS:

Drug susceptibility testing; MGIT960; Pyrazinamide; Resistance; Tuberculosis; pncA

PMID:
26071666
DOI:
10.1016/j.tube.2015.05.013
[Indexed for MEDLINE]

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