title: Genotypic analysis of isoniazid and rifampin resistance in drug-resistant clinical Mycobacterium tuberculosis complex isolates in southern Turkey.
abstract: In this study we aimed to learn about the nature and frequency of katG, inhA, and rpoB gene mutations underlying isoniazid (INH) and rifampin (RMP) resistance in clinical Mycobacterium tuberculosis complex isolates. The Silver Sequence DNA sequencing method was used to detect the resistance condition of 22 INH, 6 RMP, and 13 INH and RMP in previously determined drug-resistant clinical M. tuberculosis isolates. Thirty of 35 (85.7%) INH-resistant strains and 14 of 19 (73%) RMP-resistant strains were found to have a mutation in the analyzed katG gene fragment or inhA locus and rpoB gene fragment. In the katG gene region, the codons of mutation detected were determined to be 315 (23 of 30, 76.6%), 279 (4 of 30, 13.3%) and 293 (1 of 30, 3.3%), a finding that has not been reported previously. Our findings demonstrated that the most frequent mutation pattern was Ser315Thr at codon 315 with a rate of 60% (18 of 30). In 5 (16.6%) isolates, a nucleotide change was detected which is associated with INH resistance from -15(th) C to T in the inhA locus. In the rpoB gene region, codons possesing point mutations were 531 (9 of 14, 64.2%), 516 (1 of 14, 7.1%), 524 (1 of 14, 7.1%), and 545 (4 of 14, 28.6%), which has not been reported previously. We believe about that our present study supplies important data on the different kinds of mutations occurring at various target loci for associated RMP and INH resistance in clinical isolates of our restricted region.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Mersin, Mersin, Turkey. drgaslan@mersin.edu.tr
authors.forename: Gonul
authors.initials: G
authors.lastname: Aslan
authors.forename: Seda
authors.initials: S
authors.lastname: Tezcan
authors.forename: Mehmet Sami
authors.initials: MS
authors.lastname: Serin
authors.forename: Gurol
authors.initials: G
authors.lastname: Emekdas
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002374:Catalase / Q000235:genetics; D003062:Codon / Q000235:genetics; D004269:DNA, Bacterial / Q000032:analysis; D012321:DNA-Directed RNA Polymerases; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D010088:Oxidoreductases / Q000235:genetics; D016133:Polymerase Chain Reaction; D012293:Rifampin / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology / Q000382:microbiology; D014421:Turkey / Q000453:epidemiology
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D003062:Codon; D004269:DNA, Bacterial; C505805:rpoB protein, Mycobacterium tuberculosis; D010088:Oxidoreductases; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; C085257:InhA protein, Mycobacterium; D012321:DNA-Directed RNA Polymerases; D007538:Isoniazid; D012293:Rifampin