[Detection of S315T mutation in the katg gene as a strategy for identification of isoniazid-resistant Mycobacterium tuberculosis in a reference laboratory]

Rev Chilena Infectol. 2012 Dec;29(6):607-13. doi: 10.4067/S0716-10182012000700004.
[Article in Spanish]

Abstract

Introduction: The emergence of strains of Mycobacterium tuberculosis resistant to drugs is a public health problem.

Aim: To characterize the resistance to isoniazid (INH) in M. tuberculosis.

Methods: Phenotypic and genotypic methods were used to determine the contribution of mutations at 315 codon of katG gene to the phenotypic expression of resistance. The analysis of susceptibility to antibiotics was performed by the proportional method of Canetti and nitrate reductase method.Genotypic analysis of INH resistance was performed by PCR-RFLP.

Results: 193 strains of M. tuberculosis from patients with respiratory symptoms were analyzed. Nineteen (9.8%) strains resistant to INH were identified, of which 12 (63.2%) showed resistance to other drugs. Genotypic analysis allowed to detect the mutation S315T in the katG gene in 15 of 17 strains phenotypically resistant to INH, showing a sensitivity of 88.24%, 100% specificity, 100% positive predictive value, 92% negative predictive value and high concordance with phenotypic methods (kappa = 0.85 (p < 0.01).

Conclusion: The S315T mutation in the katG gene is the predominant mechanism of INH resistance in our circulating strains. This feature could be used as a rapid diagnostic tool with potential to detect at least 88% of isoniazid resistant strains, with great impact on the therapeutic management of patients.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology*
  • Bacterial Proteins / genetics*
  • Catalase / genetics*
  • Drug Resistance, Bacterial / genetics*
  • Genotype
  • Isoniazid / pharmacology*
  • Microbial Sensitivity Tests
  • Mutation / genetics*
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / genetics*
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length

Substances

  • Antitubercular Agents
  • Bacterial Proteins
  • Catalase
  • katG protein, Mycobacterium tuberculosis
  • Isoniazid