title: Multiple mutations in katG and inhA identified in Thai isoniazid-resistant Mycobacterium tuberculosis isolates.
abstract: 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 Arg463Leu, 7 at either Ser315Thr or Arg463Leu) while the other 4 isoniazid-resistant isolates had single point mutation only at Arg463Leu. Seven of 25 multi-drug-resistant isolates [4 at C(-15)T, 1 at T(-8)C; 1 at C(-15)T plus Ser94Ala and 1 at Ile21Val] and 2 of 4 isoniazid-resistant isolates [1 at C(-15)T, 1 at C (-15)T plus Ile21Thr] had mutations in inhA promoter and open reading frame, while the other 20 isolates had no mutation at any position. No frame shift mutation was observed in any tested isolates. This is the first report of two mutations, Trp308Pro of katG and T (-8)C of inhA in Mycobacterium tuberculosis isolates.
authors.affiliation: Department of Microbiology and Immunology, Mahidol University, Bangkok, Thailand.
authors.forename: Dhruba Kumar
authors.initials: DK
authors.lastname: Khadka
authors.forename: Boonchuay
authors.initials: B
authors.lastname: Eampokalap
authors.forename: Jarinee
authors.initials: J
authors.lastname: Panitchakorn
authors.forename: Pongrama
authors.initials: P
authors.lastname: Ramasoota
authors.forename: Srisin
authors.initials: S
authors.lastname: Khusmith
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D002374:Catalase / Q000235:genetics*; D017931:DNA Primers; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D009154:Mutation / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013785:Thailand; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000235:genetics / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D017931:DNA Primers; D010088:Oxidoreductases; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; C085257:InhA protein, Mycobacterium; D007538:Isoniazid