Abstract：
Staphylococcus aureus causes both hospital- and community-acquired infections in humans worldwide. Due to the high incidence of infection, S. aureus is also one of the most sampled and sequenced pathogens today, providing an outstanding resource to understand variation at the bacterial subspecies level. We processed and downsampled 83,383 public S. aureus Illumina whole-genome shotgun sequences and 1,263 complete genomes to produce 7,954 representative substrains. Pairwise comparison of average nucleotide identity revealed a natural boundary of 99.5% that could be used to define 145 distinct strains within the species. We found that intermediate frequency genes in the pangenome (present in 10%-95% of genomes) could be divided into those closely linked to strain background (\"strain-concentrated\") and those highly variable within strains (\"strain-diffuse\"). Non-core genes had different patterns of chromosome location. Notably, strain-diffuse genes were associated with prophages; strain-concentrated genes were associated with the vSaβ genome island and rare genes (<10% frequency) concentrated near the origin of replication. Antibiotic resistance genes were enriched in the strain-diffuse class, while virulence genes were distributed between strain-diffuse, strain-concentrated, core, and rare classes. This study shows how different patterns of gene movement help create strains as distinct subspecies entities and provide insight into the diverse histories of important S. aureus functions.
OBJECTIVE: We analyzed the genomic diversity of Staphylococcus aureus, a globally prevalent bacterial species that causes serious infections in humans. Our goal was to build a genetic picture of the different strains of S. aureus and which genes may be associated with them. We reprocessed >84,000 genomes and subsampled to remove redundancy. We found that individual samples sharing >99.5% of their genome could be grouped into strains. We also showed that a portion of genes that are present in intermediate frequency in the species are strongly associated with some strains but completely absent from others, suggesting a role in strain specificity. This work lays the foundation for understanding individual gene histories of the S. aureus species and also outlines strategies for processing large bacterial genomic data sets.
OBJECTIVE: We analyzed the genomic diversity of Staphylococcus aureus, a globally prevalent bacterial species that causes serious infections in humans. Our goal was to build a genetic picture of the different strains of S. aureus and which genes may be associated with them. We reprocessed >84,000 genomes and subsampled to remove redundancy. We found that individual samples sharing >99.5% of their genome could be grouped into strains. We also showed that a portion of genes that are present in intermediate frequency in the species are strongly associated with some strains but completely absent from others, suggesting a role in strain specificity. This work lays the foundation for understanding individual gene histories of the S. aureus species and also outlines strategies for processing large bacterial genomic data sets.
摘要：
金黄色葡萄球菌在全球范围内引起人类的医院和社区获得性感染。由于感染的高发,金黄色葡萄球菌也是当今采样和测序最多的病原体之一，为了解细菌亚种水平的变异提供了杰出的资源。我们对83,383个公共金黄色葡萄球菌Illumina全基因组shot弹枪序列和1,263个完整基因组进行了处理和下采样，以产生7,954个代表性的子序列。平均核苷酸同一性的成对比较揭示了99.5%的天然边界,其可用于定义物种内的145个不同菌株。我们发现pangenome中的中频基因（存在于10％-95％的基因组中）可以分为与菌株背景密切相关的基因（“菌株集中”）和在菌株内高度可变的基因（“菌株扩散”）。非核心基因具有不同的染色体定位模式。值得注意的是,菌株扩散基因与原抗原相关；菌株集中的基因与vSaβ基因组岛相关，稀有基因（<10％频率）集中在复制起点附近。抗生素抗性基因在菌株扩散类中富集，而毒力基因分布在菌株之间-扩散，应变集中，核心,罕见的课程。这项研究表明，不同的基因运动模式如何帮助创建菌株作为不同的亚种实体，并提供对重要金黄色葡萄球菌功能的不同历史的见解。
目的：我们分析了金黄色葡萄球菌的基因组多样性，一种全球流行的细菌物种，会导致人类严重感染。我们的目标是建立金黄色葡萄球菌不同菌株的基因图景，以及哪些基因可能与它们相关。我们对>84,000个基因组进行了重新处理，并进行了二次采样以消除冗余。我们发现共享其基因组>99.5%的个体样品可以被分组为菌株。我们还表明，在该物种中以中频存在的一部分基因与某些菌株密切相关，但与其他菌株完全不存在。表明在菌株特异性中的作用。这项工作为理解金黄色葡萄球菌物种的个体基因历史奠定了基础，并概述了处理大型细菌基因组数据集的策略。
目的：我们分析了金黄色葡萄球菌的基因组多样性，一种全球流行的细菌物种，会导致人类严重感染。我们的目标是建立金黄色葡萄球菌不同菌株的基因图景，以及哪些基因可能与它们相关。我们对>84,000个基因组进行了重新处理，并进行了二次采样以消除冗余。我们发现共享其基因组>99.5%的个体样品可以被分组为菌株。我们还表明，在该物种中以中频存在的一部分基因与某些菌株密切相关，但与其他菌株完全不存在。表明在菌株特异性中的作用。这项工作为理解金黄色葡萄球菌物种的个体基因历史奠定了基础，并概述了处理大型细菌基因组数据集的策略。
