秘鲁肺结核患者广泛耐药结核分枝杆菌临床分离株的遗传多样性特征分析
Characterization of the genetic diversity of extensively-drug resistant Mycobacterium tuberculosis clinical isolates from pulmonary tuberculosis patients in Peru.
作者信息
Cáceres Omar, Rastogi Nalin, Bartra Carlos, Couvin David, Galarza Marco, Asencios Luis, Mendoza-Ticona Alberto
机构信息
Biotechnology and Molecular Biology Laboratory, Instituto Nacional de Salud, Lima, Peru.
WHO Supranational TB Reference Laboratory, TB and Mycobacteria Unit, Institut Pasteur de la Guadeloupe, Guadeloupe, France.
出版信息
PLoS One. 2014 Dec 9;9(12):e112789. doi: 10.1371/journal.pone.0112789. eCollection 2014.
BACKGROUND
Peru holds the fourth highest burden of tuberculosis in the Americas. Despite an apparently well-functioning DOTS control program, the prevalence of multidrug resistant tuberculosis (MDR-TB) continues to increase. To worsen this situation, cases of extensively drug resistance tuberculosis (XDR-TB) have been detected. Little information exists about the genetic diversity of drug-susceptible vs. MDR-TB and XDR-TB.
METHODS
Cryopreserved samples of XDR strains from 2007 to 2009 (second semester), were identified and collected. Starting from 227 frozen samples, a total of 142 XDR-TB strains of Mycobacterium tuberculosis complex (MTBC; 1 isolate per patient) were retained for this study. Each strain DNA was analyzed by spoligotyping and the 15-loci Mycobacterial Interspersed Repetitive Unit (MIRU-15).
RESULTS
Among the 142 isolates analyzed, only 2 samples (1.41%) could not be matched to any lineage. The most prevalent sublineage was Haarlem (43.66%), followed by T (27.46%), LAM (16.2%), Beijing (9.15%), and X clade (1.41%). Spoligotype analysis identified clustering for 128/142 (90.1%) isolates vs. 49/142 (34.5%) with MIRUs. Of the samples, 90.85% belonged to retreated patients. The drug resistant profile demonstrated that 62.67% showed resistance to injectable drugs capreomycin (CAP) and kanamycin (KAN) vs. 15.5% to CAP alone and 21.8% to KAN alone. The SIT219/T1 and SIT50/H3 were the most prevalent patterns in our study. The spoligoforest analysis showed that SIT53/T1 was at the origin of many of the T lineage strains as well as a big proportion of Haarlem lineage strains (SIT50/H3, followed by SIT47/H1, SIT49/H3, and SIT2375/H1), as opposed to the SIT1/Beijing strains that did not appear to evolve into minor Beijing sublineages among the XDR-TB strains.
CONCLUSION
In contrast with other Latin-American countries where LAM sublineage is the most predominant, we found the Haarlem to be the most common followed by T sublineage among the XDR-TB strains.
背景
秘鲁是美洲结核病负担第四高的国家。尽管其直接观察短程治疗（DOTS）控制项目看似运作良好，但耐多药结核病（MDR - TB）的患病率仍在持续上升。更糟糕的是，已检测到广泛耐药结核病（XDR - TB）病例。关于药物敏感型结核病与耐多药结核病和广泛耐药结核病的基因多样性，现有信息很少。
方法
对2007年至2009年（下半年）的广泛耐药菌株的冷冻保存样本进行鉴定和收集。从227份冷冻样本开始，本研究共保留了142株结核分枝杆菌复合群（MTBC）的广泛耐药结核病菌株（每位患者1株分离株）。对每个菌株的DNA进行间隔寡核苷酸分型（spoligotyping）和15位点分枝杆菌插入重复单元（MIRU - 15）分析。
结果
在分析的142株分离株中，只有2个样本（1.41%）无法匹配到任何谱系。最常见的亚谱系是哈勒姆（Haarlem，43.66%），其次是T（27.46%）、LAM（16.2%）、北京（Beijing，9.15%）和X进化枝（1.41%）。间隔寡核苷酸分型分析显示，128/142（90.1%）的分离株存在聚类，而MIRU分析中有49/142（34.5%）的分离株存在聚类。在这些样本中，90.85%属于复治患者。耐药谱显示，62.67%的菌株对注射用药物卷曲霉素（CAP）和卡那霉素（KAN）耐药，而单独对CAP耐药的为15.5%，单独对KAN耐药的为21.8%。SIT219/T1和SIT50/H3是我们研究中最常见的模式。间隔寡核苷酸分型森林分析表明，SIT53/T1是许多T谱系菌株以及很大一部分哈勒姆谱系菌株（SIT50/H3，其次是SIT47/H1、SIT49/H3和SIT2375/H1）的起源，而SIT1/北京菌株在广泛耐药结核病菌株中似乎没有进化成较小的北京亚谱系。
结论
与其他以LAM亚谱系最为 predominant的拉丁美洲国家不同，我们发现哈勒姆亚谱系在广泛耐药结核病菌株中最为常见，其次是T亚谱系。 （注：原文中“predominant”拼写错误，正确拼写应为“predominant”，这里按正确意思翻译为“最为常见的”）
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