High Prevalence of KatG Ser315Thr Substitution among Isoniazid-Resistant <i>Mycobacterium tuberculosis</i> Clinical Isolates from Northwestern Russia, 1996 to 2001

DOI Web Site 被引用文献3件
  • Igor Mokrousov
    Laboratory of Molecular Microbiology, St. Petersburg Pasteur Institute
  • Olga Narvskaya
    Laboratory of Molecular Microbiology, St. Petersburg Pasteur Institute
  • Tatiana Otten
    Microbiology Laboratory, The Research Institute of Phthisiopulmonology
  • Elena Limeschenko
    Laboratory of Molecular Microbiology, St. Petersburg Pasteur Institute
  • Lidia Steklova
    City Anti-Tuberculosis Dispensary, St. Petersburg, Russia
  • Boris Vyshnevskiy
    Microbiology Laboratory, The Research Institute of Phthisiopulmonology

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<jats:title>ABSTRACT</jats:title> <jats:p> A total of 204 isoniazid (INH)-resistant strains of <jats:italic>Mycobacterium tuberculosis</jats:italic> isolated from different patients in the northwestern region of Russia from 1996 to 2001 were screened by a PCR-restriction fragment length polymorphism (RFLP) assay. This assay uses <jats:italic>Hap</jats:italic> II cleavage of an amplified fragment of the <jats:italic>katG</jats:italic> gene to detect the transversion 315AGC→ACC (Ser→Thr), which is associated with INH resistance. This analysis revealed a 93.6% prevalence of the <jats:italic>katG</jats:italic> S315T mutation in strains from patients with both newly and previously diagnosed cases of tuberculosis (TB). This mutation was not found in any of 57 INH-susceptible isolates included in the study. The specificity of the assay was 100%; all isolates that contained the S315T mutation were classified as resistant by a culture-based susceptibility testing method. The Beijing genotype, defined by IS <jats:italic>6110</jats:italic> -RFLP analysis and the spacer oligonucleotide typing (spoligotyping) method, was found in 60.3% of the INH-resistant strains studied. The <jats:italic>katG</jats:italic> S315T shift was more prevalent among Beijing genotype strains than among non-Beijing genotype strains: 97.8 versus 84.6%, respectively, for all isolates, including those from patients with new and previously diagnosed cases, isolated from 1999 to 2001 and 100.0 versus 86.5%, respectively, for isolates from patients with new cases isolated from 1996 to 2001. The design of this PCR-RFLP assay allows the rapid and unambiguous identification of the <jats:italic>katG</jats:italic> 315ACC mutant allele. The simplicity of the assay permits its implementation into routine practice in clinical microbiology laboratories in regions with a high incidence of TB where this mutation is predominant, including northwestern Russia. </jats:p>

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