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首页> 外文期刊>Journal of bacteriology >Mosaic Prophages with Horizontally Acquired Genes Account for the Emergence and Diversification of the Globally Disseminated M1T1 Clone of Streptococcus pyogenes
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Mosaic Prophages with Horizontally Acquired Genes Account for the Emergence and Diversification of the Globally Disseminated M1T1 Clone of Streptococcus pyogenes

机译：水平获取基因的马赛克噬菌体解释了化脓性链球菌的全球传播的M1T1克隆的出现和多样化。

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The recrudescence of severe invasive group A streptococcal (GAS) diseases has been associated with relatively few strains, including the M1T1 subclone that has shown an unprecedented global spread and prevalence and high virulence in susceptible hosts. To understand its unusual epidemiology, we aimed to identify unique genomic features that differentiate it from the fully sequenced M1 SF370 strain. We constructed DNA microarrays from an M1T1 shotgun library and, using differential hybridization, we found that both M1 strains are 95% identical and that the 5% unique M1T1 clone sequences more closely resemble sequences found in the M3 strain, which is also associated with severe disease. Careful analysis of these unique sequences revealed three unique prophages that we named M1T1.X, M1T1.Y, and M1T1.Z. While M1T1.Y is similar to phage 370.3 of the M1-SF370 strain, M1T1.X and M1T1.Z are novel and encode the toxins SpeA2 and Sda1, respectively. The genomes of these prophages are highly mosaic, with different segments being related to distinct streptococcal phages, suggesting that GAS phages continue to exchange genetic material. Bioinformatic and phylogenetic analyses revealed a highly conserved open reading frame (ORF) adjacent to the toxins in 18 of the 21 toxin-carrying GAS prophages. We named this ORF paratox, determined its allelic distribution among different phages, and found linkage disequilibrium between particular paratox alleles and specific toxin genes, suggesting that they may move as a single cassette. Based on the conservation of paratox and other genes flanking the toxins, we propose a recombination-based model for toxin dissemination among prophages. We also provide evidence that a minor population of the M1T1 clonal isolates have exchanged their virulence module on phage M1T1.Y, replacing it with a different module identical to that found on a related M3 phage. Taken together, the data demonstrate that mosaicism of the GAS prophages has contributed to the emergence and diversification of the M1T1 subclone.
机译：严重的A组侵袭性链球菌（GAS）疾病的复发与相对较少的菌株相关，包括M1T1亚克隆，该亚克隆在易感宿主中显示出空前的全球传播和流行以及高毒力。为了了解其不寻常的流行病学，我们旨在鉴定独特的基因组特征，以区别于完全测序的M1 SF370菌株。我们从M1T1 shot弹枪文库中构建了DNA微阵列，并使用差异杂交技术，发现这两个M1菌株都具有95％的同一性，而5％的独特M1T1克隆序列与M3菌株中发现的序列更相似，这也与疾病。对这些独特序列的仔细分析揭示了三个独特的预言，我们将其命名为M1T1.X，M1T1.Y和M1T1.Z。虽然M1T1.Y与M1-SF370菌株的噬菌体370.3类似，但M1T1.X和M1T1.Z是新颖的，分别编码毒素SpeA2和Sda1。这些噬菌体的基因组是高度镶嵌的，不同区段与独特的链球菌噬菌体有关，这表明GAS噬菌体继续交换遗传物质。生物信息学和系统发育分析表明，在21种携带毒素的GAS噬菌体中，有18种与毒素相邻，具有高度保守的开放阅读框（ORF）。我们将其命名为ORF寄生虫，确定其在不同噬菌体之间的等位基因分布，并发现特定的寄生虫等位基因与特定的毒素基因之间的连锁不平衡，表明它们可能作为单个盒移动。基于对毒素和侧翼毒素的其他基因的保守性，我们提出了一种基于重组的模型，用于在噬菌体之间传播毒素。我们还提供了证据，表明少数M1T1克隆分离株已在噬菌体M1T1.Y上交换了其毒性模块，并用与相关M3噬菌体相同的模块替换了它。综上所述，数据表明，GAS噬菌体的镶嵌性促进了M1T1亚克隆的出现和多样化。

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