Characterization of pncA mutations of pyrazinamide-resistant Mycobacterium tuberculosis in Turkey

Pelin Yüksel1, Ozlem Tansel

  • 1Medical Faculty of Trakya University, Department of Clinical Microbiology and Infectious Diseases, Edirne, Turkey.

Insights

Mutations in the pyrazinamidase (PZase) gene (pncA) are a primary cause of pyrazinamide (PZA) resistance in Mycobacterium tuberculosis. This study identified novel pncA mutations and a frameshift deletion in Turkish strains, contributing to understanding PZA resistance mechanisms.

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • Pyrazinamide (PZA) is a crucial first-line drug for treating Mycobacterium tuberculosis infections.
  • Resistance to PZA is often mediated by mutations in the pyrazinamidase (PZase) gene (pncA).

Purpose of the Study:

  • To investigate pncA mutations in PZA-resistant and susceptible Mycobacterium tuberculosis strains from Turkey.
  • To correlate genotypic findings with pyrazinamidase enzyme activity.

Main Methods:

  • Bacterial identification using BACTEC NAP.
  • Drug susceptibility testing via the BACTEC system.
  • Molecular analysis including PCR-RFLP and DNA sequencing for pncA mutations.

Main Results:

  • No pncA mutations were found in susceptible strains or three resistant strains.
  • Identified known mutations (Gly24Asp, Thr160Lys, His51Pro) in resistant strains.
  • Discovered two new mutations and a 167 bp frameshift deletion at nucleotide position 102 in resistant strains.

Conclusions:

  • pncA mutations are key drivers of PZA resistance in Mycobacterium tuberculosis.
  • This study identified novel mutations and a frameshift deletion, expanding the known spectrum of PZA resistance mechanisms.
  • Findings contribute to a better understanding of genotypic-phenotypic correlations in PZA resistance.

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