Staphylococcus aureus is a colonizing opportunistic pathogen and a leading cause of bloodstream infection with high morbidity and mortality. S. aureus carriage frequency is reportedly between 20 and 40 % among healthy adults, with S. aureus colonization considered to be a risk factor for S. aureus bacteraemia. It is unknown whether a genetic component of the bacterium is associated with S. aureus bacteraemia in comparison to nasal carriage strains. Previous association studies primarily focusing on the clinical outcome of an S. aureus infection have produced conflicting results, often limited by study design challenged by sample collections and the clonal diversity of S. aureus . To date, no study has investigated whether genomic features separate nasal carriage isolates from S. aureus bacteraemia isolates within a single clonal lineage. Here we have investigated whether genomic features, including single-nucleotide polymorphisms (SNPs), genes, or kmers, distinguish S. aureus nasal carriage isolates from bacteraemia isolates that all belong to the same clonal lineage [clonal complex 45 (CC45)] using whole-genome sequencing (WGS) and a genome-wide association (GWA) approach. From CC45, 100 isolates (50 bacteraemia and 50 nasal carriage, geographically and temporally matched) from Denmark were whole-genome sequenced and subjected to GWA analyses involving gene copy number variation, SNPs, gene content, kmers and gene combinations, while correcting for lineage effects. No statistically significant association involving SNPs, specific genes, gene variants, gene copy number variation, or a combination of genes was identified that could distinguish bacteraemia isolates from nasal carriage isolates. The presented results suggest that all S. aureus nasal CC45 isolates carry the potential to cause invasive disease, as no core or accessory genome content or variations were statistically associated with invasiveness.

中文翻译：

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金黄色葡萄球菌克隆复合体 45 分离株的基因组分析无法区分鼻携带菌和菌血症。


金黄色葡萄球菌是一种定植的机会性病原体，也是导致高发病率和死亡率的血流感染的主要原因。据报道，健康成年人中金黄色葡萄球菌携带频率为 20% 至 40%，金黄色葡萄球菌定植被认为是金黄色葡萄球菌菌血症的危险因素。与鼻携带菌株相比，尚不清楚该细菌的遗传成分是否与金黄色葡萄球菌菌血症有关。先前主要关注金黄色葡萄球菌感染的临床结果的关联研究产生了相互矛盾的结果，通常受到样本收集和金黄色葡萄球菌克隆多样性挑战的研究设计的限制。迄今为止，还没有研究调查基因组特征是否将鼻携带分离株与单一克隆谱系内的金黄色葡萄球菌菌血症分离株分开。在这里，我们使用全基因组特征（包括单核苷酸多态性 (SNP)、基因或 kmers）研究了是否可以将金黄色葡萄球菌鼻携带分离株与属于同一克隆谱系 [克隆复合体 45 (CC45)] 的菌血症分离株区分开来。 -基因组测序（WGS）和全基因组关联（GWA）方法。 从 CC45 中，对来自丹麦的 100 个分离株（50 个菌血症和 50 个鼻携带，地理和时间匹配）进行了全基因组测序，并进行了 GWA 分析，涉及基因拷贝数变异、SNP、基因内容、kmers 和基因组合，同时校正谱系影响。没有发现涉及单核苷酸多态性（SNP）、特定基因、基因变异、基因拷贝数变异或基因组合的统计显着关联可以区分菌血症分离株和鼻携带分离株。所提出的结果表明，所有金黄色葡萄球菌鼻腔 CC45 分离株均具有引起侵袭性疾病的潜力，因为没有核心或辅助基因组内容或变异与侵袭性具有统计相关性。