Mycobacterium tuberculosis Beijing Lineage Favors the Spread of Multidrug-Resistant Tuberculosis in the Republic of Georgia

Mycobacterium tuberculosis Beijing Lineage Favors the Spread of Multidrug-Resistant Tuberculosis in the Republic of Georgia
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DOI:
10.1128/jcm.00715-10
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发表时间:
2010-10-01
影响因子:
9.4
通讯作者:
Tang, Yi-Wei
Tang, Yi-Wei
中科院分区:
医学2区
文献类型:
--
作者:
Niemann, Stefan;Diel, Roland;Tang, Yi-Wei

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多药耐药(MDR)结核病(TB)的高发率和传播与结核分枝杆菌复合体(MTBC)北京谱系有关,这表明病原体遗传因素对感染结果和流行病学的调节具有重要意义。在此,我们对来自格鲁吉亚共和国的MTBC菌株的种群结构进行了深入分析,格鲁吉亚共和国是黑海沿岸的一个高发病率地区。通过24位点MIRU-VNTR(分枝杆菌穿插重复单位可变数串联重复序列)和spoligotyping分析确定了系统发育谱系。确定具有相同基因型谱的病毒群作为近期传播率的指标。在调查的183株结核分枝杆菌中,北京株(26%)最为突出,其次是LAM株(18%)、Ural株(12%)和Haarlem株(5%)。一个密切相关的未定义的系统发育类群(62株)显示出与实验室菌株H37RV相似的基因分型模式,被命名为“乔治亚-H37RV样”。虽然在不同菌株系中均发现异烟肼耐药,但耐多药结核病几乎完全局限于北京菌株(P < 0.0001)。约50%的分离株呈聚集性,表明近期传播率很高。我们的数据表明,除了证实北京基因型菌株对前苏联国家结核病流行病学的重要性外,LAM、乌拉尔、哈勒姆菌株和以前未定义的谱系的高种群多样性占格鲁吉亚发现的菌株的近三分之二。在既往治疗和耐多药结核病患者中,较高的发病率表明北京谱系逃避治疗并发展为耐多药结核病的可能性更高。
High rates and transmission of multidrug-resistant (MDR) tuberculosis (TB) have been associated with the Mycobacterium tuberculosis complex (MTBC) Beijing lineage, pointing to the importance of pathogen genetic factors for the modulation of infection outcome and epidemiology. We present here an in-depth analysis of the population structure of MTBC strains from the Republic of Georgia, a high-incidence setting at the Black Sea Coast. Phylogenetic lineages were identified based on 24-locus MIRU-VNTR (for mycobacterial interspersed repetitive unit-variable number tandem repeat) and spoligotyping analysis. Clusters of strains with identical genotyping profiles were determined as an indicator for the rate of recent transmission. Among the 183 M. tuberculosis isolates investigated, the most prominent lineage found was Beijing (26%), followed by the LAM (18%), Ural (12%), and Haarlem (5%) strains. A closely related previously undefined phylogenetic group (62 strains) showed a genotyping pattern similar to laboratory strain H37RV and was denominated as "Georgia-H37RV-like." Although isoniazid resistance was found among strains of different lineages, MDR TB was nearly completely restricted to Beijing strains (P < 0.0001). Approximately 50% of the isolates were grouped in clusters, indicating a high rate of recent transmission. Our data indicate that, in addition to the confirmation of the importance of Beijing genotype strains for the TB epidemiology in former Soviet Union countries, a high-population diversity with strains of the LAM, Ural, Haarlem, and a previously undefined lineage represents nearly two-thirds of the strains found in Georgia. Higher rates among previously treated and MDR TB patients point to a higher potential of lineage Beijing to escape therapy and develop MDR TB.