[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.


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.
Ano
Hiromi
H
Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, 3-7-1, Habikino, Habikino-shi, Osaka 583-8588, Japan. ano@zeus.eonet.ne.jp
Matsumoto
Tomoshige
T
Nagai
Takayuki
T
Tamura
Yoshitaka
Y
Yoshida
Hiroko
H
Kawahara
Kunimitsu
K
Takamatsu
Isamu
I
Tsuyuguchi
Izuo
I
Takashima
Tetsuya
T
D000995:Antitubercular Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D020411:Oligonucleotide Array Sequence Analysis
D000995:Antitubercular Agents; D007538:Isoniazid