M-protein and other intrinsic virulence factors of Streptococcus pyogenes are encoded on an ancient pathogenicity island.

M-protein and other intrinsic virulence factors of Streptococcus pyogenes are encoded on an ancient pathogenicity island.
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DOI:
10.1186/1471-2164-10-198
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发表时间:
2009-04-27
期刊:
影响因子:
4.4
通讯作者:
Roten CA
Roten CA
中科院分区:
生物学2区
文献类型:
--
作者:
Panchaud A;Guy L;Collyn F;Haenni M;Nakata M;Podbielski A;Moreillon P;Roten CA

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完全测序的细菌基因组数量不断增加,可以比较它们的结构和基因组成。这些新信息凸显了横向遗传交换在细菌进化和物种形成中的关键作用。在这里,我们通过一种简单的方法分析了化脓性链球菌的 12 个测序基因组,该方法检查沿染色体的优先核苷酸使用,即 G 与 C(GC 偏斜)和 T 与 A(TA 偏斜)的使用。累积GC偏斜图呈现由两个对称线性段组成的倒V形,其中最小值和最大值对应于DNA复制的起点和终点。相比之下,累积 TA 偏度呈 V 形,其片段被几个陡坡区域 (SSR) 打断,表明不同的核苷酸组成偏差。每个化脓性链球菌基因组包含多达九个单独的 SSR,涵盖所有描述的菌株特异性原噬菌体。此外,每个基因组都含有相似的独特的非噬菌体SSR,其核心由31个高度同源的基因组成。该核心包括M蛋白、其他mga相关因子和其他毒力基因,总共10个内在毒力基因。除了毒力相关基因含量高和特殊的核苷酸偏差外,M1GAS 菌株中的这种 SSR 长 47 kb,还含有直接重复序列和 tRNA 基因,表明存在可移动元件。此外,它在M蛋白阴性A组链球菌天然分离物中完全不存在,表明它可能会自发丢失,但体外缺失实验表明它的切除发生率非常低。该 SSR 的稳定性,结合其在所有已测序的化脓性链球菌测序基因组中的存在,表明它是古代获得的结果。因此,这种非吞噬性 SSR 与化脓性链球菌物种形成之前获得的致病岛相容。它的潜在切除可能与疫苗开发相关,因为针对 M 蛋白的疫苗可能会选择仍携带其他毒力决定因素的 M 蛋白阴性变体。
The increasing number of completely sequenced bacterial genomes allows comparing their architecture and genetic makeup. Such new information highlights the crucial role of lateral genetic exchanges in bacterial evolution and speciation. Here we analyzed the twelve sequenced genomes of Streptococcus pyogenes by a naïve approach that examines the preferential nucleotide usage along the chromosome, namely the usage of G versus C (GC-skew) and T versus A (TA-skew). The cumulative GC-skew plot presented an inverted V-shape composed of two symmetrical linear segments, where the minimum and maximum corresponded to the origin and terminus of DNA replication. In contrast, the cumulative TA-skew presented a V-shape, which segments were interrupted by several steep slopes regions (SSRs), indicative of a different nucleotide composition bias. Each S. pyogenes genome contained up to nine individual SSRs, encompassing all described strain-specific prophages. In addition, each genome contained a similar unique non-phage SSR, the core of which consisted of 31 highly homologous genes. This core includes the M-protein, other mga-related factors and other virulence genes, totaling ten intrinsic virulence genes. In addition to a high content in virulence-related genes and to a peculiar nucleotide bias, this SSR, which is 47 kb-long in a M1GAS strain, harbors direct repeats and a tRNA gene, suggesting a mobile element. Moreover, its complete absence in a M-protein negative group A Streptococcus natural isolate demonstrates that it could be spontaneously lost, but in vitro deletion experiments indicates that its excision occurred at very low rate. The stability of this SSR, combined to its presence in all sequenced S. pyogenes sequenced genome, suggests that it results from an ancient acquisition. Thus, this non-phagic SSR is compatible with a pathogenicity island, acquired before S. pyogenes speciation. Its potential excision might bear relevance for vaccine development, because vaccines targeting M-protein might select for M-protein-negative variants that still carry other virulence determinants.
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