title: Molecular analysis of isoniazid resistance in different genotypes of Mycobacterium tuberculosis isolates from Iran.
abstract: Considering the significant increase of isoniazid (INH) resistance in Iranian Mycobacterium tuberculosis isolates in the last few years and to investigate the prevalence and diagnostic potential of the most commonly reported mutations associated with INH resistance in Iran, we analyzed parts of the katG gene and fabG1-inhA and oxyR-ahpC regulatory regions in a sample of 48 INH-resistant and 25 INH-sensitive isolates. Mutations in the katG 315, fabG1-inhA, and oxyR-ahpC regulatory regions were detected in 58.3%, 18.7%, and 39.6% of isolates, respectively. The R463L polymorphism in the katG gene and the ahpC46A were detected with high frequency in both INH-resistant and -sensitive isolates. Spoligotyping and IS6110-based restriction fragment length polymorphism patterns revealed that most of the isolates containing ahpC46A and katG 463Leu polymorphism belonged to the Central Asian (CAS) super family. The tight relationship between ahpC46A and katG 463Leu polymorphisms and the CAS super family highlights the importance of the CAS super family in INH resistance in Iran. In conclusion, mutations at katG codon 315 or the fabG1-inhA regulatory region were identified in 77.0% of the INH-resistant isolates and in none of the INH-sensitive strains, and are highly predictive of isonizid resistance in Iranian isolates.
authors.affiliation: Department of Microbiology, School of Medicine, and Infectious and Tropical Diseases Research Center, Ahwaz JundiShapour University of Medical Sciences, Ahwaz, Iran.
authors.forename: Farahnoosh
authors.initials: F
authors.lastname: Doustdar
authors.forename: Azar Dokht
authors.initials: AD
authors.lastname: Khosravi
authors.forename: Parissa
authors.initials: P
authors.lastname: Farnia
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Masjedi
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Velayati
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007492:Iran / Q000453:epidemiology; D007538:Isoniazid / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D010088:Oxidoreductases / Q000235:genetics; D010544:Peroxidases / Q000235:genetics; D054464:Peroxiredoxins / Q000235:genetics; D011237:Predictive Value of Tests; D017422:Sequence Analysis, DNA; D014376:Tuberculosis / Q000453:epidemiology / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D010088:Oxidoreductases; D010544:Peroxidases; D054464:Peroxiredoxins; C076136:catalase HPI; C085257:InhA protein, Mycobacterium; D007538:Isoniazid