title: Characterisation of pyrazinamide-resistant Mycobacterium tuberculosis strains isolated in Poland and Germany.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Napiórkowska
authors.affiliation: The National Reference Centre for Mycobacteria, Forschungszentrim Borstel, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Rüsch-Gerdes
authors.affiliation: The National Reference Centre for Mycobacteria, Forschungszentrim Borstel, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Hillemann
authors.affiliation: The National Reference Centre for Mycobacteria, Forschungszentrim Borstel, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Richter
authors.affiliation: Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Augustynowicz-Kopeć
mesh_terms: D000581:Amidohydrolases / Q000235:genetics*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001431:Bacteriological Techniques; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005838:Genotype; D005858:Germany; D006801:Humans; D008826:Microbial Sensitivity Tests; D018598:Minisatellite Repeats; D017720:Molecular Epidemiology; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D010641:Phenotype; D011044:Poland; D012150:Polymorphism, Restriction Fragment Length; D011718:Pyrazinamide / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission
chemical_list: D000995:Antitubercular Agents; D004269:DNA, Bacterial; D011718:Pyrazinamide; D000581:Amidohydrolases; C487496:PncA protein, Mycobacterium tuberculosis