Genetic and phenotypic characterization of pyrazinamide-resistant Mycobacterium tuberculosis complex isolates in Japan
Genetic and phenotypic characterization of pyrazinamide-resistant Mycobacterium tuberculosis complex isolates in Japan
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DOI：
10.1016/j.diagmicrobio.2003.09.013
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发表时间：
2004-02-01
影响因子：
2.9
通讯作者：
Takashima, T
中科院分区：
文献类型：
--
作者：
Miyagi, C;Yamane, N;Takashima, T
在日本的26株结核分枝杆菌耐吡嗪酰胺（PZA）菌株中测定了与PZA耐药相关的pncA基因突变。在所包括的26个PZA耐药分离株中，21个对吡嗪酰胺酶（PZase）呈阴性。其中，20个分离株有各种pncA突变，导致改变的一级氨基酸序列。而1株PZase阴性的分离株pncA基因未发生突变。其余5株PZA耐药菌株PZase阳性，pncA等位基因与PZA敏感菌株相同。IS 6110 RFLP分析表明，IS 6110具有不同的分型，其中5对分离物的基因型非常接近（同源性>90%）。该研究表明，大多数PZA抗性是pncA上的各种突变导致PZase活性丧失的结果。进一步的调查，特别是对PZase阳性但PZA耐药的分离株和PZase阴性但pncA无突变的分离株，应立即进行。(C)2004年爱思唯尔公司All rights reserved.
The pncA gene mutations associated with pyrazinamide (PZA) resistance in Mycobacterium tuberculosis complex were determined in 26 PZA-resistant isolates in Japan. Of the 26 PZA-resistant isolates included, 21 were negative for pyrazinamidase (PZase). Of these, 20 isolates had various pncA mutations, resulting in alteration of primary amino acid sequence. However, 1 PZase-negative isolate did not have any mutation on pncA gene. The remaining 5 PZA-resistant isolates were positive for PZase and had identical pncA alleles with PZA-susceptible isolates. IS6110 RFLP analysis demonstrated various distinct IS6110 types and 5 pairs of isolates were very close to each other (>90% identical pattern). This study demonstrates that most of the PZA resistance is a result of various mutations on pncA resulting in loss of PZase activity. Further investigation, particularly on PZase-positive but PZA-resistant isolates and a PZase-negative isolate with no mutation on pncA, should be urgently done. (C) 2004 Elsevier Inc. All rights reserved.