Characterization of pncA gene mutations in pyrazinamide-resistant Mycobacterium tuberculosis isolates from Mexico

Characterization of pncA gene mutations in pyrazinamide-resistant Mycobacterium tuberculosis isolates from Mexico
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DOI:
10.1016/j.meegid.2012.12.013
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发表时间:
2013-10-01
影响因子:
3.2
通讯作者:
Zenteno-Cuevas, Roberto
Zenteno-Cuevas, Roberto
中科院分区:
医学3区
文献类型:
--
作者:
Cuevas-Cordoba, Betzaida;Oyuki Xochihua-Gonzalez, Sheila;Zenteno-Cuevas, Roberto

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许多研究已经将结核分枝杆菌中pncA基因的突变与吡嗪酰胺(Z)的耐药性联系起来。然而,这些突变的变异是分离株原产国特有的。本研究的目的是描述在M.对Z耐药的结核病,来自墨西哥的患者。从怀疑携带耐药结核病的个体中回收结核病分离株,并开发了相应的敏感性测试。对127株吡嗪酰胺耐药菌株进行pncA基因及其启动子的毛细管测序分析,发现42株(33%)对吡嗪酰胺耐药。pncA序列在34株(81%)分离株中显示26个变化:18个SNPs(n = 26,62%),4个插入(n = 4,9.5%)和4个缺失(n = 4,9.5%)。在8个(19%)序列/分离株中观察到无修饰。最常见的变化是突变L120 P(n = 7)和K96 R(n = 4)。首次报道了12个突变,这是首次描述来自墨西哥的吡嗪酰胺耐药菌株的pncA基因修饰。我们的结论是,pncA的变化的多样性表明存在一个值得注意的各种吡嗪酰胺耐药菌株发生在该地区。(C)2013年爱思唯尔B。V.保留所有权利。
Numerous studies have linked mutations in the pncA gene with resistance to pyrazinamide (Z) in Mycobacterium tuberculosis. However, variations in these mutations are specific to the country of origin of the isolate. The aim of this study was to characterize changes in pncA gene sequence in isolates of M. tuberculosis with resistance to Z, from patients in Mexico.M. tuberculosis isolates were recovered from individuals suspected of carrying drug resistant tuberculosis and respective susceptibility tests were developed. In isolates with resistance to pyrazinamide the pncA gene and its promoter were analyzed by capillary sequencing.From 127 drug-resistant isolates collected, 42 (33%) were resistant to pyrazinamide. The pncA sequences showed 26 changes in 34 (81%) isolates: 18 SNPs (n = 26, 62%), four insertions (n = 4, 9.5%) and four deletions (n = 4, 9.5%). Absence of modifications was observed in eight (19%) sequences/isolates. The most frequent changes were the mutations L120P (n = 7) and K96R (n = 4). Twelve changes found are reported for the first time.This is the first description of pncA gene modifications in pyrazinamide resistant isolates originating in Mexico. We conclude that the diversity of changes in pncA indicates the presence of a noteworthy variety of pyrazinamide resistant strains occurring in the area. (C) 2013 Elsevier B. V. All rights reserved.