1887

Abstract

Drug-resistant tuberculosis poses a significant problem for treatment. The mechanisms of resistance to the front-line drug isoniazid (INH) are complex and can be mediated by , and other unknown genes. To identify the percentage of INH-resistant strains with no or mutation, this study characterized a panel of 28 clinical isolates of and five mutants derived from H37Rv resistant to INH. Seventeen of 33 resistant strains (51 %) had mutations with 12 of the 17 strains having the most common KatG Ser315Thr mutation. Three of the 17 strains with the KatG 315 mutation had an additional mutation in the promoter and were resistant to a high level of INH. Seventeen of the 33 INH-resistant strains (51 %) had mutations. The most common promoter mutation was −15C→T and was present in 13 of the 17 mutations. This promoter mutation occurred alone without mutations and was associated with a low level of INH and ethionamide resistance. However, other mutations were associated with mutations. No mutations were found in the gene. Three of 33 strains (9 %) had no mutations in , or , indicating that their resistance was due to a new mechanism of resistance. Detection of the KatG Ser315Thr mutation and the −15C→T mutation accounted for 76 % (25/33) of the INH-resistant strains and should be useful for rapid detection of INH-resistant strains by molecular tests.

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2006-11-01
2024-04-19
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