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

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


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / genetics*
  • Antitubercular Agents / therapeutic use*
  • Bacteriological Techniques*
  • DNA Mutational Analysis*
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Extensively Drug-Resistant Tuberculosis / diagnosis*
  • Extensively Drug-Resistant Tuberculosis / drug therapy
  • Extensively Drug-Resistant Tuberculosis / epidemiology
  • Extensively Drug-Resistant Tuberculosis / microbiology
  • Genotype
  • Humans
  • Microbial Sensitivity Tests
  • Mutation*
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / isolation & purification
  • Mycobacterium tuberculosis / pathogenicity
  • Phenotype
  • Predictive Value of Tests
  • Prevalence
  • Pyrazinamide / therapeutic use*
  • Russia / epidemiology
  • Tuberculosis, Multidrug-Resistant / diagnosis*
  • Tuberculosis, Multidrug-Resistant / drug therapy
  • Tuberculosis, Multidrug-Resistant / epidemiology
  • Tuberculosis, Multidrug-Resistant / microbiology


  • Antitubercular Agents
  • Pyrazinamide
  • Amidohydrolases
  • PncA protein, Mycobacterium tuberculosis