Mutations in the pyrazinamidase (PZase) gene (pncA) are considered the major mechanism of pyrazinamide (PZA) resistance in Mycobacterium tuberculosis. The aim of this study was designed to determine pncA mutations among ten PZA resistant and two PZA susceptible M. tuberculosis strains from Turkey and also to compare the PZase activity of them with the genotype. All isolates were identified by BACTEC NAP (P-nitro-alpha-acetylamino-beta-hydroxy-propiophenone)test and PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) method. Drug sensitivity tests were performed by BACTEC system. PncA mutations were detected by DNA sequence analysis. No mutation was detected in two PZA susceptible and three out of tell PZA resistant strains. While, two of the PZA resistant strains had mutations in the same region (Gly24Asp), two of the PZA resistant strains had mutations in different regions (Thr160Lys), (His51Pro). Three of the PZA resistant strains had frameshift as a 167 bp deletion at nucleotide position 102. As a result, we detected two new mutations and a frameshift which may be responsible for PZA resistance in this study different from the other studies which previously 51st codon mutation was reported.

This study was supported by Government Planning Organization (Project No: 2002KI20500). Project a. title is 'Determination of mutation against major anti-tuberculosis drugs in M. tuberculosis bacilli by DNA sequencing analysis in Turkey'. The authors thank Prof. Dr. Ahmet Sani for technical support.

Government Planning Organization [2002KI20500]