Bouchiat Coralie, Moreau Karen, Devillard Sébastien, Rasigade Jean-Philippe, Mosnier Amandine, Geissmann Tom, Bes Michèle, Tristan Anne, Lina Gérard, Laurent Frédéric, Piroth Lionel, Aissa Nejla, Duval Xavier, Le Moing Vincent, Vandenesch François
Laboratoire de Bactériologie, Centre de Biologie Est, Hospices Civils de Lyon, 59 Boulevard Louis Pinel, 69677 Bron Cedex, France; CIRI, International Center for Infectiology Research, Inserm U1111, Université Lyon 1, Ecole Normale Supérieure de Lyon, CNRS UMR5308, 7 rue Guillaume Paradin, 69008 Lyon, France; Centre National de Référence des Staphylocoques, 59 Boulevard Louis Pinel, 69677 Bron Cedex, France.
CIRI, International Center for Infectiology Research, Inserm U1111, Université Lyon 1, Ecole Normale Supérieure de Lyon, CNRS UMR5308, 7 rue Guillaume Paradin, 69008 Lyon, France.
Infect Genet Evol. 2015 Dec;36:524-530. doi: 10.1016/j.meegid.2015.08.029. Epub 2015 Aug 28.
Infective endocarditis (IE)((1)) is a severe condition complicating 10-25% of Staphylococcus aureus bacteremia. Although host-related IE risk factors have been identified, the involvement of bacterial features in IE complication is still unclear. We characterized strictly defined IE and bacteremia isolates and searched for discriminant features. S. aureus isolates causing community-acquired, definite native-valve IE (n=72) and bacteremia (n=54) were collected prospectively as part of a French multicenter cohort. Phenotypic traits previously reported or hypothesized to be involved in staphylococcal IE pathogenesis were tested. In parallel, the genotypic profiles of all isolates, obtained by microarray, were analyzed by discriminant analysis of principal components (DAPC)((2)). No significant difference was observed between IE and bacteremia strains, regarding either phenotypic or genotypic univariate analyses. However, the multivariate statistical tool DAPC, applied on microarray data, segregated IE and bacteremia isolates: IE isolates were correctly reassigned as such in 80.6% of the cases (C-statistic 0.83, P<0.001). The performance of this model was confirmed with an independent French collection IE and bacteremia isolates (78.8% reassignment, C-statistic 0.65, P<0.01). Finally, a simple linear discriminant function based on a subset of 8 genetic markers retained valuable performance both in study collection (86.1%, P<0.001) and in the independent validation collection (81.8%, P<0.01). We here show that community-acquired IE and bacteremia S. aureus isolates are genetically distinct based on subtle combinations of genetic markers. This finding provides the proof of concept that bacterial characteristics may contribute to the occurrence of IE in patients with S. aureus bacteremia.
感染性心内膜炎（IE）（(1)）是一种严重病症，在10% - 25%的金黄色葡萄球菌菌血症病例中并发。尽管已确定了与宿主相关的IE危险因素，但细菌特征在IE并发症中的作用仍不清楚。我们对严格定义的IE和菌血症分离株进行了特征分析，并寻找鉴别特征。作为法国多中心队列研究的一部分，前瞻性收集了导致社区获得性、明确的天然瓣膜IE（n = 72）和菌血症（n = 54）的金黄色葡萄球菌分离株。对先前报道或假设参与葡萄球菌IE发病机制的表型特征进行了检测。同时，通过微阵列获得的所有分离株的基因型谱，采用主成分判别分析（DAPC）((2))进行分析。在表型或基因型单变量分析方面，IE和菌血症菌株之间未观察到显著差异。然而，应用于微阵列数据的多变量统计工具DAPC将IE和菌血症分离株区分开来：在80.6%的病例中，IE分离株被正确重新分类（C统计量0.83，P < 0.001）。该模型的性能在一组独立的法国IE和菌血症分离株中得到了证实（重新分类率78.8%，C统计量0.65，P < 0.01）。最后，基于8个遗传标记子集的简单线性判别函数在研究样本集（86.1%，P < 0.001）和独立验证样本集中（81.8%，P < 0.01）均保持了有价值的性能。我们在此表明，基于遗传标记的微妙组合，社区获得性IE和菌血症金黄色葡萄球菌分离株在基因上是不同的。这一发现提供了概念证明，即细菌特征可能促成金黄色葡萄球菌菌血症患者发生IE。
