Outputs of different GWAS analyses.

Human activities such as agriculturalization and domestication have led to the emergence of many new pathogens via host-switching events between humans, domesticated and wild animals. Staphylococcus aureus is a multi-host opportunistic pathogen with a global healthcare and economic burden. Recently, it was discovered that laboratory and wild rodents can be colonised and infected with S. aureus, but the origins and zoonotic potential of rodent S. aureus is unknown. In order to trace their evolutionary history, we employed a dataset of 1249 S. aureus genome sequences including 393 of isolates from rodents and other small mammals (including newly determined sequences for 305 isolates from 7 countries). Among laboratory mouse populations, we identified multiple widespread rodent-specific S. aureus clones that likely originated in humans. Phylogeographic analysis of the most common murine lineage CC88 suggests that it emerged in the 1980s in laboratory mouse facilities most likely in North America, from where it spread to institutions around the world, via the distribution of mice for research. In contrast, wild rodents (mice, voles, squirrels) were colonized with a unique complement of S. aureus lineages that are widely disseminated across Europe. In order to investigate the molecular basis for S. aureus adaptation to rodent hosts, genome-wide association analysis was carried out revealing a unique complement of bacteriophages associated with a rodent host ecology. Of note, we identified novel prophages and pathogenicity islands in rodent-derived S. aureus that conferred the potential for coagulation of rodent plasma, a key phenotype of abscess formation and persistence. Our findings highlight the remarkable capacity of S. aureus to expand into new host populations, driven by the acquisition of genes promoting survival in new host-species.

农业化与家畜驯化等人类活动，通过人类、驯养动物与野生动物之间的宿主转换事件（host-switching events），促成了大量新型病原体的出现。金黄色葡萄球菌（Staphylococcus aureus）是一种多宿主机会性致病菌，给全球医疗与经济带来了沉重负担。近期研究发现，实验啮齿动物与野生啮齿动物均可被该菌定殖并感染，但啮齿动物源金黄色葡萄球菌的起源及其人畜共患病潜力（zoonotic potential）仍未明确。为追溯其进化历史，本研究采用了包含1249株金黄色葡萄球菌基因组序列的数据集，其中393株分离自啮齿动物与其他小型哺乳动物（包括来自7个国家的305株分离株的新测定序列）。在实验小鼠种群中，我们鉴定出多个广泛传播的啮齿动物特异性金黄色葡萄球菌克隆株，其大概率起源于人类宿主。针对最常见的小鼠谱系CC88开展的系统地理分析（phylogeographic analysis）显示，该谱系于20世纪80年代出现在北美地区的实验小鼠设施中，并通过实验用小鼠的流通传播至全球各研究机构。与之形成对比的是，野生啮齿动物（小鼠、田鼠、松鼠）定殖有一套独特的金黄色葡萄球菌谱系，这些谱系在欧洲大陆广泛分布。为探究金黄色葡萄球菌适应啮齿动物宿主的分子基础，本研究开展了全基因组关联分析（genome-wide association analysis），鉴定出与啮齿动物宿主生态相关的独特噬菌体（bacteriophages）组。值得注意的是，我们在啮齿动物源金黄色葡萄球菌中发现了新型前噬菌体（prophages）与致病岛（pathogenicity islands），这些遗传元件赋予了菌株凝固啮齿动物血浆的能力——这是脓肿形成与持续感染的关键表型。本研究结果凸显了金黄色葡萄球菌通过获取促进其在新宿主物种中存活的基因，从而拓展至新宿主种群的卓越能力。