The complexity and diversity of the Pathogenicity Locus in Clostridium difficile clade 5.
The complexity and diversity of the Pathogenicity Locus in Clostridium difficile clade 5.
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DOI：
10.1093/gbe/evu248
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发表时间：
2014-11-08
影响因子：
3.3
通讯作者：
Riley TV
中科院分区：
文献类型：
--
作者：
Elliott B;Dingle KE;Didelot X;Crook DW;Riley TV
艰难梭菌感染的症状是由两种密切相关的毒素TcdA和TcdB引起的，它们由19.6 kb致病性基因座（PaLoc）编码。PaLoc在菌株中不连续存在，在这方面，它类似于一个移动的遗传元件。梭difficile种群结构主要由5个系统发育分支组成，命名为1-5。进化枝5的某些基因型与最近出现的引起人类疾病和动物感染的高致病性菌株相关。本研究的目的是探讨C. difficile clade 5.进化枝5 PaLoc变异体和相邻基因组区域的系统发育分析和注释进行了具有代表性的收集的转基因和非转基因菌株。比较进化枝5和其他进化枝的代表获得的核心基因组和PaLoc同源性，确定了两个不同的PaLoc获得事件，一个涉及毒素A+B+ PaLoc变体，另一个涉及A-B+变体。虽然每个PaLoc收购的确切机制尚不清楚，可能与其他分支和分支5谱系之间的同源重组的证据被发现内的PaLoc和邻近地区。通过与其他进化枝的PaLoc阴性成员同源重组，PaLoc丢失产生的非同源性变体通过cdu 2分析提出，尽管最近可能没有发生。在进化枝5 A−B+ PaLoc中存在的一个假定的holin基因的变体可能是通过与未知元件的等位基因交换获得的。细尺度系统发育分析。difficile进化枝5揭示了其遗传多样性的程度，与古老的进化起源和复杂的进化历史的PaLoc一致。
The symptoms of Clostridium difficile infection are caused by two closely related toxins, TcdA and TcdB, which are encoded by the 19.6 kb Pathogenicity Locus (PaLoc). The PaLoc is variably present among strains, and in this respect it resembles a mobile genetic element. The C. difficile population structure consists mainly of five phylogenetic clades designated 1–5. Certain genotypes of clade 5 are associated with recently emergent highly pathogenic strains causing human disease and animal infections. The aim of this study was to explore the evolutionary history of the PaLoc in C. difficile clade 5. Phylogenetic analyses and annotation of clade 5 PaLoc variants and adjoining genomic regions were undertaken using a representative collection of toxigenic and nontoxigenic strains. Comparison of the core genome and PaLoc phylogenies obtained for clade 5 and representatives of the other clades identified two distinct PaLoc acquisition events, one involving a toxin A+B+ PaLoc variant and the other an A−B+ variant. Although the exact mechanism of each PaLoc acquisition is unclear, evidence of possible homologous recombination with other clades and between clade 5 lineages was found within the PaLoc and adjacent regions. The generation of nontoxigenic variants by PaLoc loss via homologous recombination with PaLoc-negative members of other clades was suggested by analysis of cdu2, although none is likely to have occurred recently. A variant of the putative holin gene present in the clade 5 A−B+ PaLoc was likely acquired via allelic exchange with an unknown element. Fine-scale phylogenetic analysis of C. difficile clade 5 revealed the extent of its genetic diversity, consistent with ancient evolutionary origins and a complex evolutionary history for the PaLoc.