Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
Bioinformatics Core, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
PLoS Pathog. 2021 Feb 5;17(2):e1009304. doi: 10.1371/journal.ppat.1009304. eCollection 2021 Feb.
S. epidermidis is a substantial component of the human skin microbiota, but also one of the major causes of nosocomial infection in the context of implanted medical devices. We here aimed to advance the understanding of S. epidermidis genotypes and phenotypes conducive to infection establishment. Furthermore, we investigate the adaptation of individual clonal lines to the infection lifestyle based on the detailed analysis of individual S. epidermidis populations of 23 patients suffering from prosthetic joint infection. Analysis of invasive and colonizing S. epidermidis provided evidence that invasive S. epidermidis are characterized by infection-supporting phenotypes (e.g. increased biofilm formation, growth in nutrient poor media and antibiotic resistance), as well as specific genetic traits. The discriminating gene loci were almost exclusively assigned to the mobilome. Here, in addition to IS256 and SCCmec, chromosomally integrated phages was identified for the first time. These phenotypic and genotypic features were more likely present in isolates belonging to sequence type (ST) 2. By comparing seven patient-matched nasal and invasive S. epidermidis isolates belonging to identical genetic lineages, infection-associated phenotypic and genotypic changes were documented. Besides increased biofilm production, the invasive isolates were characterized by better growth in nutrient-poor media and reduced hemolysis. By examining several colonies grown in parallel from each infection, evidence for genetic within-host population heterogeneity was obtained. Importantly, subpopulations carrying IS insertions in agrC, mutations in the acetate kinase (AckA) and deletions in the SCCmec element emerged in several infections. In summary, these results shed light on the multifactorial processes of infection adaptation and demonstrate how S. epidermidis is able to flexibly repurpose and edit factors important for colonization to facilitate survival in hostile infection environments.
表皮葡萄球菌是人体皮肤微生物群的重要组成部分，但也是植入医疗器械相关医院感染的主要原因之一。我们旨在深入了解有利于感染建立的表皮葡萄球菌基因型和表型。此外，我们通过对 23 名患有人工关节感染的患者的个体表皮葡萄球菌群体的详细分析，研究了个体克隆系适应感染生活方式的情况。对侵袭性和定植性表皮葡萄球菌的分析表明，侵袭性表皮葡萄球菌具有支持感染的表型（例如增加生物膜形成、在营养贫瘠的培养基中生长和抗生素耐药性）以及特定的遗传特征。有区别的基因座几乎完全被分配到可移动元件。除了 IS256 和 SCCmec 之外，还首次在染色体上鉴定到整合噬菌体。这些表型和基因型特征在属于序列型 (ST)2 的分离物中更为常见。通过比较属于相同遗传谱系的 7 名患者匹配的鼻腔和侵袭性表皮葡萄球菌分离物，记录了与感染相关的表型和基因型变化。除了生物膜形成增加外，侵袭性分离物还具有更好的在营养贫瘠的培养基中生长和减少溶血的特性。通过平行检查从每个感染中生长的多个菌落，获得了宿主内遗传群体异质性的证据。重要的是，在几个感染中，agrC 中的 IS 插入、乙酸激酶 (AckA) 突变和 SCCmec 元件缺失的亚群出现了。总之，这些结果阐明了感染适应的多因素过程，并展示了表皮葡萄球菌如何灵活地重新利用和编辑对定植很重要的因素，以促进在恶劣的感染环境中的生存。
