Genetic and phenotypic characterization of pyrazinamide-resistant mycobacterium tuberculosis complex isolates in Japan

The pncA gene mutations associated with pyrazinamide (PZA) resistance in Mycobacterium tuberculosis complex were determined in 26 PZA-resistant isolates in Japan. Of the 26 PZA-resistant isolates included, 21 were negative for pyrazinamidase (PZase). Of these, 20 isolates had various pncA mutations,...

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Published in:Diagnostic microbiology and infectious disease 2004-02, Vol.48 (2), p.111-116
Main Authors: Miyagi, Chika, Yamane, Nobuhisa, Yogesh, Bhusal, Ano, Hiromi, Takashima, Tetsuya
Format: Article
Language:English
Subjects:
Amidohydrolases - genetics
Amidohydrolases - metabolism
Antitubercular Agents - pharmacology
Biological and medical sciences
DNA Fingerprinting
DNA Transposable Elements - genetics
DNA, Bacterial - chemistry
DNA, Bacterial - genetics
Drug Resistance, Bacterial
Fundamental and applied biological sciences. Psychology
Humans
Infectious diseases
Japan
Medical sciences
Microbiology
Mutation
Mycobacterium tuberculosis
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - enzymology
Mycobacterium tuberculosis - genetics
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Pyrazinamide - pharmacology
Tuberculosis - microbiology
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Summary:The pncA gene mutations associated with pyrazinamide (PZA) resistance in Mycobacterium tuberculosis complex were determined in 26 PZA-resistant isolates in Japan. Of the 26 PZA-resistant isolates included, 21 were negative for pyrazinamidase (PZase). Of these, 20 isolates had various pncA mutations, resulting in alteration of primary amino acid sequence. However, 1 PZase-negative isolate did not have any mutation on pncA gene. The remaining 5 PZA-resistant isolates were positive for PZase and had identical pncA alleles with PZA-susceptible isolates. IS 6110 RFLP analysis demonstrated various distinct IS 6110 types and 5 pairs of isolates were very close to each other (>90% identical pattern). This study demonstrates that most of the PZA resistance is a result of various mutations on pncA resulting in loss of PZase activity. Further investigation, particularly on PZase-positive but PZA-resistant isolates and a PZase-negative isolate with no mutation on pncA, should be urgently done.
ISSN:0732-8893
1879-0070
DOI:10.1016/j.diagmicrobio.2003.09.013