Characterization of pncA mutations of pyrazinamide-resistant Mycobacterium tuberculosis in Turkey.
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 ten 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.
Yüksel
Pelin
P
Medical Faculty of Trakya University, Department of Clinical Microbiology and Infectious Diseases, Edirne, Turkey.
Tansel
Ozlem
O
D000581:Amidohydrolases / Q000235:genetics*; D019943:Amino Acid Substitution; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use; D004269:DNA, Bacterial / Q000032:analysis / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D011718:Pyrazinamide / Q000494:pharmacology* / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000382:microbiology*; D014421:Turkey
D000995:Antitubercular Agents; D004269:DNA, Bacterial; D011718:Pyrazinamide; D000581:Amidohydrolases; C487496:PncA protein, Mycobacterium tuberculosis