Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance.
Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance.
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DOI：
10.1038/ng.3767
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发表时间：
2017-03
期刊：
影响因子：
30.8
通讯作者：
Earl AM
中科院分区：
文献类型：
--
作者：
Manson AL;Cohen KA;Abeel T;Desjardins CA;Armstrong DT;Barry CE 3rd;Brand J;TBResist Global Genome Consortium;Chapman SB;Cho SN;Gabrielian A;Gomez J;Jodals AM;Joloba M;Jureen P;Lee JS;Malinga L;Maiga M;Nordenberg D;Noroc E;Romancenco E;Salazar A;Ssengooba W;Velayati AA;Winglee K;Zalutskaya A;Via LE;Cassell GH;Dorman SE;Ellner J;Farnia P;Galagan JE;Rosenthal A;Crudu V;Homorodean D;Hsueh PR;Narayanan S;Pym AS;Skrahina A;Swaminathan S;Van der Walt M;Alland D;Bishai WR;Cohen T;Hoffner S;Birren BW;Earl AM
由结核分枝杆菌耐药菌株引起的耐多药结核病（MDR-TB）是一个日益严重的世界性问题。在这项研究中，我们检查了5，310 M的数据集。结核病全基因组序列来自五大洲。尽管在地理隔离点、遗传背景和耐药性方面存在很大差异，但耐药性出现的模式在全球范围内是保守的。我们已经确定了往往先于MDR的先兆突变。特别是，katG S315 T突变，赋予异烟肼耐药，绝大多数出现在利福平耐药之前，在所有谱系，地理区域和时间段。仅包括利福平耐药标记的分子诊断不足以识别前MDR菌株。将前MDR多态性的知识，特别是katG S315，应用于分子诊断学，将能够对前MDR-TB患者进行靶向治疗，以防止MDR-TB的进一步发展。
Multidrug-resistant tuberculosis (MDR-TB), caused by drug resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. In this study, we examined a dataset of 5,310 M. tuberculosis whole genome sequences from five continents. Despite great diversity with respect to geographic point of isolation, genetic background and drug resistance, patterns of drug resistance emergence were conserved globally. We have identified harbinger mutations that often precede MDR. In particular, the katG S315T mutation, conferring resistance to isoniazid, overwhelmingly arose before rifampicin resistance across all lineages, geographic regions, and time periods. Molecular diagnostics that include markers for rifampicin resistance alone will be insufficient to identify pre-MDR strains. Incorporating knowledge of pre-MDR polymorphisms, particularly katG S315, into molecular diagnostics will enable targeted treatment of patients with pre-MDR-TB to prevent further development of MDR-TB.