title: High level isoniazid resistance correlates with multiple mutation in the katG encoding catalase proxidase of pulmonary tuberculosis isolates from the frontier localities of Iran.
abstract: 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).
authors.affiliation: Islamic Azad University, Parand Branch, Biology and Microbiology Department, Iran. saeid1976@mail.ru
authors.forename: Saeed Z
authors.initials: SZ
authors.lastname: Bostanabad
authors.forename: Seyed Ali
authors.initials: SA
authors.lastname: Nojoumi
authors.forename: Esmaeil
authors.initials: E
authors.lastname: Jabbarzadeh
authors.forename: Mehdi
authors.initials: M
authors.lastname: Shekarabei
authors.forename: Hassan
authors.initials: H
authors.lastname: Hoseinaei
authors.forename: Mohammad K
authors.initials: MK
authors.lastname: Rahimi
authors.forename: Mostafa
authors.initials: M
authors.lastname: Ghalami
authors.forename: Shahin
authors.initials: S
authors.lastname: Pourazar Dizji
authors.forename: Evgeni R
authors.initials: ER
authors.lastname: Sagalchyk
authors.forename: Leonid P
authors.initials: LP
authors.lastname: Titov
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000235:genetics*; D002374:Catalase / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006801:Humans; D007492:Iran; D007538:Isoniazid / Q000494:pharmacology* / Q000627:therapeutic use; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; D007538:Isoniazid