Open AccessIdentification of katG Mutations Associated with High-Level Isoniazid Resistance in Mycobacterium tuberculosis
Author(s) -
Hiromitsu Ando,
Yuji Kondo,
Toshinori Suetake,
Emiko Toyota,
Seiya Kato,
Toru Mori,
Teruo Kirikae
Publication year - 2010
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01691-09
Subject(s) - isoniazid , mycobacterium tuberculosis , mutant , tuberculosis , microbiology and biotechnology , drug resistance , biology , point mutation , mutation , virology , gene , medicine , genetics , pathology
Isoniazid (INH) is an effective first-line antituberculosis drug. KatG, a catalase-peroxidase, converts INH to an active form inMycobacterium tuberculosis , andkatG mutations are major causes of INH resistance. In the present study, we sequencedkatG of 108 INH-resistantM. 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-resistantM. tuberculosis isolates.