Three-Dimensional Model and Molecular Mechanism ofMycobacterium tuberculosisCatalase-Peroxidase (KatG) and Isoniazid-Resistant KatG Mutants

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Isoniazid activation defects in recombinant Mycobacterium tuberculosis catalase-peroxidase (KatG) mutants evident in InhA inhibitor production.

Mycobacterium tuberculosis KatG catalyzes the activation of the antitubercular agent isoniazid to yield an inhibitor targeting enoyl reductase (InhA). However, no firm biochemical link between many KatG variants and isoniazid resistance has been established. In the present study, six distinct KatG variants identified in clinical Mycobacterium tuberculosis isolates resistant to isoniazid were ge...

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Multiple mutations in katG and inhA identified in Thai isoniazid-resistant Mycobacterium tuberculosis isolates.

A total of 29 Thai multi-drug-resistant/isoniazid-resistant Mycobacterium tuberculosis isolates were analyzed for mutations in katG from codons 254 to 549, inhA promoter and inhA open reading frame by DNA sequencing and single strand conformation polymorphism. Twenty-five multi-drug resistant isolates exhibited single point mutations (17 isolates at Ser315Thr plus Arg463Leu, 1 at Thr308Pro plus...

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Detection of KatG/inhA Mutation to Guide Isoniazid and Ethionamide Use for Drug-resistant Tuberculosis

BACKGROUND Depending on the presence of mutations that determine isoniazid (INH) susceptibility (katG and inhA), Mycobacterium tuberculosis may be susceptible to high doses of INH or ethionamide (ETH). OBJECTIVE To describe the INH resistance profile and association of katG mutation with previous INH treatment and level of drug resistance based on rapid molecular drug susceptibility testing (...

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Virulence in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis from south India

Isoniazid, is the only antituberculous drug for which the relation between lack of virulence and acquisition of resistance was associated. INH-resistant mutants were shown to contain defective katG gene. Classical studies showed that INH-resistant south Indian isolates have lower virulence in guinea pigs and higher susceptibility to H2O2. It is of interest to assess the virulence in south India...

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Mutations in katG gene sequences in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis are rare.

In this study, a battery of oligonucleotides was directed toward the katG gene and PCR-single-stranded conformation polymorphism (SSCP) analysis was used to search for katG gene deviations in clinical isolates of Mycobacterium tuberculosis from different geographical regions. Since a complete deletion of the katG gene was not found, it is suggested that deletion is not a major mechanism of ison...

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ژورنال

عنوان ژورنال: Microbial Drug Resistance

سال: 2004

ISSN: 1076-6294,1931-8448

DOI: 10.1089/mdr.2004.10.269