Resistance-conferring mutations of Mycobacterium tuberculosis strains with low level resistance to isoniazid

OBJECTIVE: We investigated the prevalence of isoniazid (INH) resistance-conferring mutations in the INH-indeterminate Mycobacterium tuberculosis (MTB) strains. MATERIALS AND METHODS: We initially selected a sample of 47 clinical isolates of MTB from patients, who visited the Osaka Prefectural Medical Center for Respiratory and Allergic Diseases from 2000 to 2005. Strains resistant to the concentration of 1 - 2 microg/ml were defined as "indeterminate". INH resistance-conferring mutations were determined by DNA microarray. RESULTS: Of 47 INH-indeterminate strains, only 13 (27.7%) were found to have no resistance mutations, 23 (48.9%) had mutation within the inhA regulatory region at -15 C to T, and 2 (4.3%) had mutation within the inhA regulatory region at -8 T to A, 6 (12.8%) had mutation within the katG gene at 1778 G to A, and 3 (6.4%) had mutations within the katG gene both at 1778 G to A and at 982 T to G. CONCLUSIONS: We showed that the majority of INH-indeterminate strains have resistance-conferring mutations, which were mainly detected within the inhA regulatory region.