Evolutionary history of the Clostridium difficile pathogenicity locus.
Evolutionary history of the Clostridium difficile pathogenicity locus.
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DOI：
10.1093/gbe/evt204
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发表时间：
2014-01
影响因子：
3.3
通讯作者：
Didelot X
中科院分区：
文献类型：
--
作者：
Dingle KE;Elliott B;Robinson E;Griffiths D;Eyre DW;Stoesser N;Vaughan A;Golubchik T;Fawley WN;Wilcox MH;Peto TE;Walker AS;Riley TV;Crook DW;Didelot X
艰难梭菌感染的症状是由从其19 kb致病性基因座（PaLoc）表达的毒素引起的。PaLoc的稳定整合由其单染色体定位和其不同遗传变体的进化枝特异性表明。然而，即使在密切相关的菌株中，PaLoc也不存在，因此类似于移动的遗传元件。我们的目标是通过重建PaLoc的进化历史来解释这些明显相互矛盾的观察结果。使用C.艰难梭菌群体-代表性基因组，选自1，693个致病性（PaLoc存在）和非致病性（PaLoc不存在）分离株的集合。核心基因组和PaLoc基因组的比较表明了一个多事的进化历史，不同的PaLoc变异获得的分支后，特别是分歧。特别是，我们的数据表明一个相对较新的PaLoc收购进化枝4。通过涉及侧翼染色体序列的长同源重组事件，也发生了PaLoc DNA的交换和丢失。最近的损失事件发生在2030年前的一个进化枝1基因型。进化枝3 PaLoc的遗传组织是独特的，包含一个稳定整合的新型转座子（命名为Tn 6218），其变体被发现在多个染色体位置。Tn 6218元件与Tn 916相关，但不接合，偶尔含有赋予临床相关抗生素抗性的基因。因此，两个对比，但临床上重要的遗传因素的进化历史的特点：PaLoc，动员很少通过同源重组，和Tn 6218，动员频繁通过转座。
The symptoms of Clostridium difficile infection are caused by toxins expressed from its 19 kb pathogenicity locus (PaLoc). Stable integration of the PaLoc is suggested by its single chromosomal location and the clade specificity of its different genetic variants. However, the PaLoc is variably present, even among closely related strains, and thus resembles a mobile genetic element. Our aim was to explain these apparently conflicting observations by reconstructing the evolutionary history of the PaLoc. Phylogenetic analyses and annotation of the regions spanning the PaLoc were performed using C. difficile population-representative genomes chosen from a collection of 1,693 toxigenic (PaLoc present) and nontoxigenic (PaLoc absent) isolates. Comparison of the core genome and PaLoc phylogenies demonstrated an eventful evolutionary history, with distinct PaLoc variants acquired clade specifically after divergence. In particular, our data suggest a relatively recent PaLoc acquisition in clade 4. Exchanges and losses of the PaLoc DNA have also occurred, via long homologous recombination events involving flanking chromosomal sequences. The most recent loss event occurred ∼30 years ago within a clade 1 genotype. The genetic organization of the clade 3 PaLoc was unique in containing a stably integrated novel transposon (designated Tn6218), variants of which were found at multiple chromosomal locations. Tn6218 elements were Tn916-related but nonconjugative and occasionally contained genes conferring resistance to clinically relevant antibiotics. The evolutionary histories of two contrasting but clinically important genetic elements were thus characterized: the PaLoc, mobilized rarely via homologous recombination, and Tn6218, mobilized frequently through transposition.
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影响因子：
3.3
作者：
Didelot, Xavier;Falush, Daniel
通讯作者：
Falush, Daniel
影响因子：
5.2
作者：
Deshpande, Abhishek;Pasupuleti, Vinay;Donskey, Curtis J.
通讯作者：
Donskey, Curtis J.
DOI：
10.1126/science.1220761
发表时间：
2012-08-31
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Forsberg KJ;Reyes A;Wang B;Selleck EM;Sommer MO;Dantas G
通讯作者：
Dantas G
影响因子：
12.3
作者：
Didelot X;Eyre DW;Cule M;Ip CL;Ansari MA;Griffiths D;Vaughan A;O'Connor L;Golubchik T;Batty EM;Piazza P;Wilson DJ;Bowden R;Donnelly PJ;Dingle KE;Wilcox M;Walker AS;Crook DW;Peto TE;Harding RM
通讯作者：
Harding RM
DOI：
10.1073/pnas.0914322107
发表时间：
2010-04-20
影响因子：
11.1
作者：
He, Miao;Sebaihia, Mohammed;Parkhill, Julian
通讯作者：
Parkhill, Julian