title: Molecular characterization of isoniazid-resistant Mycobacterium tuberculosis clinical strains isolated in the Philippines.
abstract: The prevalence of mutations in the katG, inhA and oxyR-ahpC genes of isoniazid (INH)-resistant Mycobacterium tuberculosis isolates in the Philippines were determined. Of 306 M. tuberculosis isolates studied, 81 (26.5%) exhibited INH-resistance. Forty-four strains (54.3%) had mutations in the katG gene, eighteen strains (22.2%) had mutations in the putative inhA locus region, seven had mutations in both regions and five strains had mutations in the oxyR-ahpC operon. Only seven strains had no mutations. A total of 71 of the 81 (87.6%) resistant strains and 65 of the 72 (90.3%) INH sensitive randomly selected strains showed amino acid substitution in codon 463 (Arg to Leu) (88.9%). This fact supports the hypothesis that mutations at codon 463 are independent of INH-resistance and are linked to the geographical origins of the strains.
authors.affiliation: Laboratorio de Referencia de Micobacterias, Servicio de Bacteriología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, CP 28220 Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Herrera
authors.forename: Azucena
authors.initials: A
authors.lastname: Valverde
authors.forename: Pilar
authors.initials: P
authors.lastname: Saiz
authors.forename: Juan A
authors.initials: JA
authors.lastname: Sáez-Nieto
authors.forename: José L
authors.initials: JL
authors.lastname: Portero
authors.forename: M Soledad
authors.initials: MS
authors.lastname: Jiménez
mesh_terms: D019943:Amino Acid Substitution; D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002374:Catalase / Q000235:genetics; D016172:DNA Fingerprinting; D004269:DNA, Bacterial / Q000032:analysis / Q000302:isolation & purification; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D017720:Molecular Epidemiology; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D009876:Operon; D010088:Oxidoreductases / Q000235:genetics; D010679:Philippines; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D012097:Repressor Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D014376:Tuberculosis / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D012097:Repressor Proteins; D010088:Oxidoreductases; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; C085257:InhA protein, Mycobacterium; D007538:Isoniazid