Characterization of pncA mutations of pyrazinamide-resistant Mycobacterium tuberculosis in Korea.
Characterization of pncA mutations of pyrazinamide-resistant Mycobacterium tuberculosis in Korea.
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DOI：
10.3346/jkms.2001.16.5.537
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发表时间：
2001-10
影响因子：
4.5
通讯作者：
Jung KS
中科院分区：
文献类型：
--
作者：
Lee KW;Lee JM;Jung KS
吡嗪酰胺（PZA）是治疗结核分枝杆菌感染的重要药物之一。然而，越来越多的PZA耐药菌株限制了其有效性。在韩国，大多数PZA耐药菌株也表现出异烟肼和利福平耐药性，因此必须准确快速地鉴定这些耐药菌株，以有效治疗分枝杆菌感染。在这项研究中，pncA基因编码吡嗪酰胺酶的突变的特点和频率进行了研究，从韩国的PZA耐药的临床分离株。使用自动DNA测序来评估基于DNA的PZA抗性检测的有用性。在95株PZA耐药临床分离株中，92株（97%）表现出可能影响酶产生或活性的突变。突变被发现在整个pncA基因，包括上游区域。单核苷酸置换似乎是主要的突变事件（69/92），尽管也鉴定出多个置换以及核苷酸的插入和缺失。本研究中观察到的pncA突变的高频率支持了基于DNA检测PZA耐药M的有用性。结核在证实了pncA基因的分散和多样的突变特征后，自动DNA测序似乎是快速检测PZA耐药M的最佳策略。结核
Pyrazinamide (PZA) is one of the most important drugs for the treatment of Mycobacterium tuberculosis infection. However, the increasing frequency of PZA-resistant strains limits its effectiveness. In Korea, most PZA-resistant strains also exhibit both isoniazid and rifampin resistance making it essential to identify these resistant strains accurately and rapidly for effective treatment of mycobacterial infection. In this study, the characteristics and frequency of mutations of the pncA gene encoding pyrazinamidase were investigated in PZA-resistant clinical isolates from Korea. Automated DNA sequencing was used to evaluate the usefulness of DNA-based detection of PZA resistance. Among 95 PZA-resistant clinical isolates, 92 (97%) exhibited mutations potentially affecting either the production or the activity of the enzyme. Mutations were found throughout the pncA gene including the upstream region. Single nucleotide replacement appeared to be the major mutational event (69/92), although multiple substitutions as well as insertion and deletion of nucleotides were also identified. The high frequency of pncA mutations observed in this study supports the usefulness of DNA-based detection of PZA-resistant M. tuberculosis. Having verified the scattered and diverse mutational characteristics of the pncA gene, automated DNA sequencing seems to be the best strategy for rapid detection of PZA-resistant M. tuberculosis.
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