High level isoniazid resistance correlates with multiple mutation in the katG encoding catalase proxidase of pulmonary tuberculosis isolates from the frontier localities of Iran.
نویسندگان
چکیده
The aim of this study was to investigate the significance of multiple-mutations in the katG gene, predominant nucleotide changes and its correlation with high level of resistance to isoniazid in Mycobacterium tuberculosis isolates that were randomly collected from sputa of 42 patients with primary and secondary active pulmonary tuberculosis from different geographic regions of Iran. Drug susceptibility testing was determined using the CDC standard conventional proportional method. DNA extraction, katG gene amplification, and DNA sequencing analysis were performed. Thirty four (80%) isolates were found to have multiple-mutations (composed of 2-5 mutations) in the katG gene. Increased number of predominant mutations and nucleotide changes were demonstrated in codons 315 (AGC-->ACC), 316 (GGC-->AGC), 309 (GGT-->GTT) with a higher frequency among patients bearing secondary tuberculosis infection with elevated levels of resistance to isoniazid (MIC ≥ 5-10 µg/mL). Furthermore, it was demonstrated that the combination of mutations with their predominant nucleotide changes were also observed in codons 315, 316, and 309 indicating higher frequencies of mutations among patients with secondary infection respectively. In this study, 62% (n= 21) of multi-mutated isolates found to have combination of mutations with predominant nucleotide changes in codons 315 (AGC-->ACC), 316 (GGC-->GTT), 309 (GGT-->GGT), and also demonstrated to be more frequent in isolates of patients with secondary infections, bearing higher level of resistance to isoniazid (≥ 5-10 µg/mL).
منابع مشابه
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...
متن کاملIsoniazid MIC and KatG Gene Mutations among Mycobacterium tuberculosis Isolates in Northwest of Iran
Objective(s) Isoniazid (INH) is one of the main first line drugs used in treatment of tuberculosis and development of resistance against this compound can result in serious problems in treatment procedures. Resistance to INH is mediated mainly by mutation in KatG gene that is coded for the catalase enzyme. The proportional method for detection of INH-resistance is time consuming due to the slo...
متن کاملCharacterization of Mutations in the Rpob and Katg Gene of Mycobacterium Tuberculosis Isolates From Pasteur Institute of Tehran
Objective: The Rifampicin resistance and susceptibility of Mycobacterium tuberculosis are caused by mutations in the 81-base pair region of the rpoB gene encoding the b-subunit of RNA polymerase. Methods: Isoniazid resistance of M. tuberculosis is related to mutations in inha , oxyR and ahpC genes which 30 to 90 percent of Isoniazid resistance is occurred in 3015 codons of kat...
متن کاملCharacterization of Mutations in the Rpob and Katg Gene of Mycobacterium Tuberculosis Isolates From Pasteur Institute of Tehran
Objective: The Rifampicin resistance and susceptibility of Mycobacterium tuberculosis are caused by mutations in the 81-base pair region of the rpoB gene encoding the b-subunit of RNA polymerase. Methods: Isoniazid resistance of M. tuberculosis is related to mutations in inha , oxyR and ahpC genes which 30 to 90 percent of Isoniazid resistance is occurred in 3015 codons of kat...
متن کاملتشخیص موتاسیون در کدون 315 ژن katG، مارکر مقاومت به ایزونیازید در سوشهای مایکوباکتریوم توبرکولوزیس جدا شده از بیماران اصفهان و تهران با روش PCR-RFLP
Background and Objective: Drug resistance to tuberculosis is continuously increasing and is a significant threat to tuberculosis control programs because afew effective drugs are present against Mycobacterium tuberculosis. Although isoniazid (INH) is the most effective drug against tuberculosis, resistance to this drug also develops readily. Mutations in katG, specially the Ser315Thr substituti...
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ورودعنوان ژورنال:
- Tuberkuloz ve toraks
دوره 59 1 شماره
صفحات -
تاریخ انتشار 2011