Enterococcus faecium is a gut commensal of the gastro-digestive tract, but also known as nosocomial pathogen among hospitalized patients. Population genetics based on whole-genome sequencing has revealed that E. faecium strains from hospitalized patients form a distinct clade, designated as clade A1 and that plasmids are major contributors to the emergence of nosocomial E. faecium. Here we further explored the adaptive evolution of E. faecium using a genome-wide co-evolution study (GWES) to identify co-evolving SNPs. We identified three genomic regions harboring large numbers of SNPs in tight linkage which are not proximal to each other based on the completely assembled chromosome of clade A1 reference hospital isolate AUS0004. Close examination of these regions revealed that they are located at the borders of four different types of large-scale genomic rearrangements, insertion sites of two different genomic islands and an IS30-like transposon. In non-clade A1 isolates, these regions are adjacent to each other and they lack the insertions of the genomic islands and IS30-like transposon. Additionally, among the clade A1 isolates there is one group of pet isolates lacking the genomic rearrangement and insertion of the genomic islands, suggesting a distinct evolutionary trajectory. In silico analysis of the biological functions of the genes encoded in three regions revealed a common link to a stress response. This suggests that these rearrangements may reflect adaptation to the stringent conditions in the hospital environment, such as antibiotics and detergents, to which bacteria are exposed. In conclusion, to our knowledge, this is the first study using GWES to identify genomic rearrangements, suggesting that there is considerable untapped potential to unravel hidden evolutionary signals from population genomic data.

中文翻译：

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通过对主要医院病原体粪肠球菌的全基因组共进化分析发现的基因组重排

粪肠球菌是消化道的肠道标志，但在住院患者中也被称为医院病原体。基于全基因组测序的群体遗传学表明，住院患者的粪肠球菌菌株形成了一个独特的进化枝，称为进化枝A1，质粒是导致医院内粪肠球菌出现的主要因素。在这里，我们进一步使用全基因组协同进化研究（GWES）来探索粪肠球菌的适应性进化，以鉴定协同进化的SNP。我们根据进化枝A1参考医院分离株AUS0004的完全装配的染色体，鉴定了三个基因组区域，它们在紧密连接中包含大量SNP，这些基因组彼此之间并不邻近。对这些区域的仔细检查表明，它们位于四种不同类型的大规模基因组重排，两个不同基因组岛的插入位点以及一个IS30样转座子的边界。在非进化A1分离株中，这些区域彼此相邻，并且缺少基因岛和IS30样转座子的插入。另外，在进化枝A1分离株中，有一组宠物分离株缺乏基因组重排和基因组岛的插入，这暗示了独特的进化轨迹。在计算机分析中，对在三个区域编码的基因的生物学功能进行了分析，发现它们与应激反应具有共同的联系。这表明这些重排可能反映了对医院环境中严格条件的适应性，例如抗生素和清洁剂，细菌暴露于其中。总而言之，据我们所知，这是第一项使用GWES识别基因组重排的研究，表明从人口基因组数据中揭示隐藏的进化信号具有相当大的尚未开发的潜力。