Detection of mutations associated with isoniazid resistance in Mycobacterium tuberculosis isolates from China.
Nine structural genes (furA, katG, inhA, kasA, Rv0340, iniB, iniA, iniC, and efpA) and two regulatory regions (the oxyR-ahpC intergenic region and the promoter of mabA-inhA) in 87 isoniazid (INH)-monoresistant and 50 INH-susceptible Mycobacterium tuberculosis isolates collected from five provinces of China were analyzed by sequencing. Eighty-two (94.3%) INH-resistant isolates had mutations in the katG gene, with the katG Ser315Thr mutation predominant (55.2%). No mutation at codon 463 of katG was detected among the 50 INH-susceptible isolates with different IS6110 fingerprints. In addition, there were 35 (40.2%) INH-resistant isolates that had a mutation at codon 463 of katG. Of the INH-resistant strains, 20 (23.0%) isolates harbored double mutations at two separate loci of katG. Mutations in the inhA promoter region occurred in 13 (14.9%) isolates; 4.6% of the isolates had inhA structural gene mutations, and 11.5% harbored mutations in the oxyR-ahpC intergenic region. Drug resistance-associated mutations were detected in the iniBAC region and efpA.
Zhang
Min
M
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433, People's Republic of China.
Yue
Jun
J
Yang
Yan-Ping
YP
Zhang
Hong-Mei
HM
Lei
Jian-Qiang
JQ
Jin
Rui-Liang
RL
Zhang
Xue-Lian
XL
Wang
Hong-Hai
HH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000494:pharmacology*; D002681:China; D003062:Codon / Q000235:genetics; D004251:DNA Transposable Elements / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005260:Female; D005798:Genes, Bacterial / Q000235:genetics*; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*
D000995:Antitubercular Agents; D003062:Codon; D004251:DNA Transposable Elements; D007538:Isoniazid