Molecular analysis of isoniazid resistance in Mycobacterium tuberculosis isolates recovered from South Korea

Molecular analysis of isoniazid resistance in Mycobacterium tuberculosis isolates recovered from South Korea
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DOI:
10.1016/s0732-8893(03)00132-9
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发表时间:
2003-11-01
影响因子:
2.9
通讯作者:
Kang, CS
Kang, CS
中科院分区:
医学4区
文献类型:
--
作者:
Kim, SY;Park, YJ;Kang, CS

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通过测序和MspI限制性内切酶分析,检测了韩国71株异烟肼(INH)耐药结核分枝杆菌和26株INH敏感结核分枝杆菌的katG、inhA和ahpC基因。在71株INH耐药分离株中,分别检测到54.9%、2.8%、1.4%、1.4%、1.4%、19.7%和5.6%的katG 315单独突变、katG 315 + inhA突变、katG 315 + ahpC突变、katG 309单独突变、katG 309 + inhA突变、inhA突变和ahpC突变。INH单药耐药株与多重耐药株相比,这些突变的频率无统计学显著差异(p > 0.05)。katG密码子315的突变与高水平的INH耐药性(MIC,> 1 μ g/ml)相关,而inhA启动子区的突变与低水平的INH耐药性(MIC,> 0.2至1 μ g/ml)相关。在两株利福平耐药菌株中发现了先前未描述的katG密码子309的GGT->GAT(Gly->Asp)突变,包括多重耐药菌株,但我们不能评估这是否预示着INH耐药。katG密码子315和/或inhA启动子区的分子分析的敏感性和特异性分别为80.3%和100%。因此,这些区域的突变高度预测韩国的INH耐药性。(C)2003年爱思唯尔公司All rights reserved.
The katG, inhA and ahpC genes, in 71 isoniazid (INH)-resistant and 26 INH-susceptible Mycobacterium tuberculosis isolates, from South Korea were examined by sequencing and MspI restriction enzyme analysis. Mutations in the katG 315 alone, katG 315 plus inhA, katG 315 plus ahpC, katG 309 alone, katG 309 plus inhA, inhA alone, and ahpC alone, were detected in 54.9, 2.8, 1.4, 1.4, 1.4, 19.7, and 5.6% of the 71 INH-resistant isolates, respectively. There was no statistically significant difference (p > 0.05) in the frequencies of these mutations for the INH-monoresistant compared with the multidrug-resistant isolates. Mutations in the katG codon 315 were associated with the high-level of INH resistance (MIC, > 1 mug/ml), whereas the mutation in the inhA promoter region was associated with the low-level of INH resistance (MIC, > 0.2 to 1 mug/ml). The previously undescribed GGT-->GAT (Gly-->Asp) mutation in the katG codon 309 was found in two rifampin, including-multidrug-resistant isolates, but we cannot assess if this is predictive of INH resistance. The sensitivity and specificity of molecular analysis of the katG codon 315 and/or the inhA promoter region were 80.3 and 100%, respectively. Therefore, mutations in these regions are highly predictive of INH resistance in South Korea. (C) 2003 Elsevier Inc. All rights reserved.