Patterns of pncA mutations in drug-resistant Mycobacterium tuberculosis isolated from patients in South Korea
Patterns of pncA mutations in drug-resistant Mycobacterium tuberculosis isolated from patients in South Korea
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DOI：
10.5588/ijtld.10.0739
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发表时间：
2012-01-01
影响因子：
4
通讯作者：
Lee, K. H.
中科院分区：
文献类型：
--
作者：
Kim, H. J.;Kwak, H. K.;Lee, K. H.
背景技术背景：吡嗪酰胺（PZA）是一种有效的抗结核药物，当吡嗪酰胺酶（PZase）将其转化为吡嗪酸时，对结核分枝杆菌具有毒性。PZA耐药主要是由酶活性的突变的损失所引起的。目的：探讨PZA耐药分枝杆菌从韩国patients.METHODS：临床证明耐药的分枝杆菌分离株的pncA突变的模式，以确定抗结核药物的敏感性。pncA突变通过测序识别，并与相关的野生型DNA sequence.RESULTS：在108株分离株，102成功培养，并进行药物敏感性试验，所有的多药耐药（MDR）。pncA突变在86株（85.1%）培养分离株中发现：MDR中55株（84.6%）和广泛耐药分离株中31株（86.1%）。单核苷酸的取代是最常见的。最常见的突变是导致核苷酸（nt）71处移码的缺失、nt 403处的取代和nt 11处的取代。合并起来，这些占所有突变的40%。而15例PZase活性缺陷的标本（14.9%）未发现突变。结核病是来自韩国患者的MDR分离株中PZA耐药的主要机制。突变的模式可能更加分散和多样化。基于DNA的PZA耐药性诊断具有快速检测耐药性的潜力。
BACKGROUND: Pyrazinamide (PZA), one of the most effective anti-tuberculosis drugs, becomes toxic to Mycobacterium tuberculosis when converted to pyrazinoic acid by pyrazinamidase (PZase). PZA resistance is caused mainly by the loss of enzyme activity by mutation.OBJECTIVE: To investigate the patterns of pncA mutations in PZA-resistant mycobacteria isolated from South Korean patients.METHODS: Mycobacterial isolates with clinically proven drug resistance were cultured to determine susceptibility to anti-tuberculosis agents. pncA mutations were recognised by sequencing and compared with the relevant wild-type DNA sequence.RESULTS: Among 108 isolates, 102 were successfully cultured and underwent drug susceptibility testing; all were multidrug-resistant (MDR). pncA mutations were found in 86 cultured isolates (85.1%): 55 (84.6%) in MDR and 31 (86.1%) in extensively drug-resistant isolates. Substitution of a single nucleotide was most common. The most frequent mutations were a deletion that caused a frameshift at nucleotide (nt) 71, a substitution at nt 403 and a substitution at nt 11. Combined, these accounted for similar to 40% of all mutations. However, 15 samples (14.9%) with defective PZase activity showed no mutation.CONCLUSION: pncA mutation in M. tuberculosis is a major mechanism of PZA resistance in MDR isolates from patients in South Korea. The patterns of mutation might be more scattered and diverse. DNA-based diagnosis of PZA resistance has potential for the rapid detection of drug resistance.