title: Pyrazinamide resistance in Mycobacterium tuberculosis arises after rifampicin and fluoroquinolone resistance.
abstract: BACKGROUND
  Multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (TB) constitute a major public health concern.
  
  
  OBJECTIVE
  To determine the timing of pncA mutations that confer pyrazinamide (PZA) resistance in relation to mutations conferring resistance to isoniazid (INH) and rifampicin (RMP).
  
  
  METHODS
  Isolates from two major urban centres--Paris (101 strains) and Shanghai (171 strains)--were investigated for the association of pncA mutations with resistance to drugs other than PZA.
  
  
  RESULTS
  The proportion of pncA mutations found in INH-monoresistant strains was not increased.
  
  
  CONCLUSIONS
  pncA mutations associated with PZA resistance were found almost exclusively in MDR-TB strains, underlining the importance of determining PZA resistance when treating MDR- or XDR-TB.
authors.affiliation: Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France; Research and Specialised Diagnostics Unit, National Laboratory of Public Health, Libreville, Gabon.
authors.forename: A K
authors.initials: AK
authors.lastname: Alame-Emane
authors.affiliation: Key Laboratory of Medical Molecular Virology, Institutes of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: P
authors.initials: P
authors.lastname: Xu
authors.affiliation: Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France; Laboratoire de Bactériologie, Bichat-Claude Bernard Hospital, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Pierre-Audigier
authors.affiliation: Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Cadet-Daniel
authors.affiliation: Department of Tuberculosis Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Shen
authors.affiliation: Laboratoire de Bactériologie, Bichat-Claude Bernard Hospital, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Sraouia
authors.affiliation: Research and Specialised Diagnostics Unit, National Laboratory of Public Health, Libreville, Gabon.
authors.forename: J F Djoba
authors.initials: JF
authors.lastname: Siawaya
authors.affiliation: Laboratorio de Genética Molecular, Centro de Microbiologıa y Biologıa Celular, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela.
authors.forename: H
authors.initials: H
authors.lastname: Takiff
authors.affiliation: Key Laboratory of Medical Molecular Virology, Institutes of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France; Emerging Bacterial Pathogens Laboratory, Institut Pasteur of Shanghai, Shanghai, China.
authors.forename: B
authors.initials: B
authors.lastname: Gicquel
mesh_terms: D000581:Amidohydrolases / Q000235:genetics; D000995:Antitubercular Agents / Q000627:therapeutic use*; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D054908:Extensively Drug-Resistant Tuberculosis / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D024841:Fluoroquinolones / Q000627:therapeutic use*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D010297:Paris / Q000453:epidemiology; D010641:Phenotype; D011718:Pyrazinamide / Q000627:therapeutic use*; D012293:Rifampin / Q000627:therapeutic use*; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D011718:Pyrazinamide; D000581:Amidohydrolases; C487496:PncA protein, Mycobacterium tuberculosis; D012293:Rifampin