Characterisation of pyrazinamide-resistant Mycobacterium tuberculosis strains isolated in Poland and Germany

Int J Tuberc Lung Dis. 2014 Apr;18(4):454-60. doi: 10.5588/ijtld.13.0457.

Abstract

Background: Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug that is generally administered with isoniazid, rifampicin, ethambutol and streptomycin.

Objective: To analyse the correlation between phenotypic resistance to PZA and genotype to find out whether the great diversity in pncA mutations is epidemiologically useful in tracing the transmission of PZA-resistant Mycobacterium tuberculosis strains among patients.

Materials and methods: The study included 71 PZA-resistant M. tuberculosis strains isolated from 62 Polish and 9 German patients. All strains were analysed using minimal inhibitory concentration value determination, pncA mutation analysis, spoligotyping, 24-loci mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) and insertion sequence (IS) 6110 restriction fragment length polymorphism (RFLP) fingerprinting.

Results: In 63 isolates, 37 (88.7%) different mutations in the pncA gene were observed, 13 of which had not been previously reported; 11 molecular families with the same MIRU-VNTR and IS6110-RFLP pattern were found. The same mutation was identified in three families, while different ones were identified in the remaining families.

Conclusion: Mutations in the pncA gene are a major cause of PZA resistance in M. tuberculosis. pncA mutation analysis can be used to obtain valuable additional information, but should be applied with caution for epidemiological analysis.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / genetics*
  • Antitubercular Agents / therapeutic use*
  • Bacteriological Techniques
  • DNA Mutational Analysis
  • DNA, Bacterial / genetics*
  • Drug Resistance, Bacterial / genetics*
  • Genotype
  • Germany
  • Humans
  • Microbial Sensitivity Tests
  • Minisatellite Repeats
  • Molecular Epidemiology
  • Mutation*
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / genetics*
  • Mycobacterium tuberculosis / isolation & purification
  • Phenotype
  • Poland
  • Polymorphism, Restriction Fragment Length
  • Pyrazinamide / therapeutic use*
  • Tuberculosis, Pulmonary / diagnosis
  • Tuberculosis, Pulmonary / epidemiology*
  • Tuberculosis, Pulmonary / microbiology
  • Tuberculosis, Pulmonary / transmission

Substances

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