Genomic analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of Mycobacterium tuberculosis.

Genomic analysis of smooth tubercle bacilli provides insights into ancestry and pathoadaptation of Mycobacterium tuberculosis.
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DOI:
10.1038/ng.2517
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发表时间:
2013-02
期刊:
影响因子:
30.8
通讯作者:
Brosch, Roland
Brosch, Roland
中科院分区:
生物学1区
文献类型:
--
作者:
Supply, Philip;Marceau, Michael;Mangenot, Sophie;Roche, David;Rouanet, Carine;Khanna, Varun;Majlessi, Laleh;Criscuolo, Alexis;Tap, Julien;Pawlik, Alexandre;Fiette, Laurence;Orgeur, Mickael;Fabre, Michel;Parmentier, Cecile;Frigui, Wafa;Simeone, Roxane;Boritsch, Eva C.;Debrie, Anne-Sophie;Willery, Eve;Walker, Danielle;Quail, Michael A.;Ma, Laurence;Bouchier, Christiane;Salvignol, Gregory;Sayes, Fadel;Cascioferro, Alessandro;Seemann, Torsten;Barbe, Valerie;Locht, Camille;Gutierrez, Maria-Cristina;Leclerc, Claude;Bentley, Stephen D.;Stinear, Timothy P.;Brisse, Sylvain;Medigue, Claudine;Parkhill, Julian;Cruveiller, Stephane;Brosch, Roland

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全球传播和遗传单态性是结核分枝杆菌(人类结核病的病原体)的特征。相反,卡氏分枝杆菌和相关的结核杆菌也会引起人类结核病,并表现出不寻常的光滑菌落形态,仅限于东非。在这里,我们使用桑格(4- 5倍覆盖率)、454/罗氏(13- 18倍覆盖率)和/或Illumina DNA测序(4- 5 - 105倍覆盖率)对光滑结核杆菌(STB)的五种代表性菌株的基因组进行测序和分析。我们发现STB是高度重组和进化的早期分支,具有更大的基因组大小,25倍的SNP,更少的分子疤痕和不同的CRISPR-Cas系统。结核尽管存在差异,但所有引起结核病的分枝杆菌都有一个高度保守的核心基因组。小鼠感染实验表明,STB比M.结核我们的结论是M.结核病是通过获得持久性和毒力机制从一个祖先的、类似STB的分枝杆菌库中出现的,我们提供了对所涉及的分子事件的全基因组见解。
Global spread and genetic monomorphism are hallmarks of Mycobacterium tuberculosis, the agent of human tuberculosis. In contrast, Mycobacterium canettii, and related tubercle bacilli that also cause human tuberculosis and exhibit unusual smooth colony morphology, are restricted to East-Africa. Here, we sequenced and analyzed the genomes of five representative strains of smooth tubercle bacilli (STB) using Sanger (4-5x coverage), 454/Roche (13-18x coverage) and/or Illumina DNA sequencing (45-105x coverage). We show that STB are highly recombinogenic and evolutionary early-branching, with larger genome sizes, 25-fold more SNPs, fewer molecular scars and distinct CRISPR-Cas systems relative to M. tuberculosis. Despite the differences, all tuberculosis-causing mycobacteria share a highly conserved core genome. Mouse-infection experiments revealed that STB are less persistent and virulent than M. tuberculosis. We conclude that M. tuberculosis emerged from an ancestral, STB-like pool of mycobacteria by gain of persistence and virulence mechanisms and we provide genome-wide insights into the molecular events involved.
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发表时间: 2007-08-01
影响因子: 10.7
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