title: Identification of katG mutations associated with high-level isoniazid resistance in Mycobacterium tuberculosis.
abstract: Isoniazid (INH) is an effective first-line antituberculosis drug. KatG, a catalase-peroxidase, converts INH to an active form in Mycobacterium tuberculosis, and katG mutations are major causes of INH resistance. In the present study, we sequenced katG of 108 INH-resistant M. tuberculosis clinical isolates. Consequently, 9 novel KatG mutants with a single-amino-acid substitution were found. All of these mutants had significantly lower INH oxidase activities than the wild type, and each mutant showed various levels of activity. Isolates having mutations with relatively low activities showed high-level INH resistance. On the basis of our results and known mutations associated with INH resistance, we developed a new hybridization-based line probe assay for rapid detection of INH-resistant M. tuberculosis isolates.
authors.affiliation: Department of Infectious Diseases, Research Institute, International Medical Center of Japan, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ando
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kondo
authors.forename: Toshinori
authors.initials: T
authors.lastname: Suetake
authors.forename: Emiko
authors.initials: E
authors.lastname: Toyota
authors.forename: Seiya
authors.initials: S
authors.lastname: Kato
authors.forename: Toru
authors.initials: T
authors.lastname: Mori
authors.forename: Teruo
authors.initials: T
authors.lastname: Kirikae
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000995:Antitubercular Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D002374:Catalase / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008828:Microbiological Techniques; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D015345:Oligonucleotide Probes / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D015345:Oligonucleotide Probes; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; D007538:Isoniazid