Linezolid-resistant Enterococcus faecalis (LREfs) carrying optrA are increasingly reported globally from multiple sources, but we lack a comprehensive analysis of human and animal optrA-LREfs strains. To assess if optrA is dispersed in isolates with varied genetic backgrounds or with common genetic features, we investigated the phylogenetic structure, genetic content [antimicrobial resistance (AMR), virulence, prophages, plasmidome] and optrA-containing platforms of 27 publicly available optrA-positive E. faecalis genomes from different hosts in seven countries. At the genome-level analysis, an in-house database with 64 virulence genes was tested for the first time. Our analysis showed a diversity of clones and adaptive gene sequences related to a wide range of genera from Firmicutes . Phylogenies of core and accessory genomes were not congruent, and at least PAI-associated and prophage genes contribute to such differences. Epidemiologically unrelated clones (ST21, ST476-like and ST489) obtained from human clinical and animal hosts in different continents over eight years (2010–2017) could be phylogenetically related (3–126 SNPs difference). optrA was located on the chromosome within a Tn6674-like element (n=10) or on medium-size plasmids (30–60 kb; n=14) belonging to main plasmid families (RepA_N/Inc18/Rep_3). In most cases, the immediate gene vicinity of optrA was generally identical in chromosomal (Tn6674) or plasmid (impB-fexA-optrA) backbones. Tn6674 was always inserted into the same ∆radC integration site and embedded in a 32 kb chromosomal platform common to strains from different origins (patients, healthy humans, and animals) in Europe, Africa, and Asia during 2012–2017. This platform is conserved among hundreds of E. faecalis genomes and proposed as a chromosomal hotspot for optrA integration. The finding of optrA in strains sharing common adaptive features and genetic backgrounds across different hosts and countries suggests the occurrence of common and independent genetic events occurring in distant regions and might explain the easy de novo generation of optrA-positive strains. It also anticipates a dramatic increase of optrA carriage and spread with a serious impact on the efficacy of linezolid for the treatment of Gram-positive infections.

中文翻译：

---

全球携带optrA的粪肠球菌的比较基因组学揭示了在核心和辅助基因组多样性中获取optrA的常见染色体热点。

全球范围内越来越多地报道了携带optrA的耐利奈唑胺的屎肠球菌（LREfs）的来源，但我们缺乏对人和动物optrA -LREfs菌株的全面分析。为了评估optrA是否分散在具有不同遗传背景或具有共同遗传特征的分离物中，我们调查了27种可公开获得的optrA-的系统发育结构，遗传成分[抗微生物剂（AMR），毒力，噬菌体，质粒组]和包含optrA的平台-积极粪肠球菌 来自七个国家/地区的不同宿主的基因组。在基因组水平的分析中，首次测试了具有64个毒力基因的内部数据库。我们的分析表明，与Firmicutes的广泛属有关的克隆和适应基因序列的多样性。核心和辅助基因组的系统发育不一致，并且至少PAI相关基因和噬菌体基因促成这种差异。在八年内（2010-2017年）从不同大陆的人类临床和动物宿主获得的与流行病学无关的克隆（ST21，ST476-like和ST489）可能是系统发育相关的（3–126个SNPs差异）。optrA位于Tn 6674样元件内的染色体上（n = 10）或属于主要质粒家族（RepA_N / Inc18 / Rep_3）的中等大小质粒（30-60 kb；n = 14）。在大多数情况下，在染色体（Tn 6674）或质粒（impB-fexA-optrA）骨架中，optrA的直接基因附近通常相同。在2012–2017年期间，Tn 6674始终插入相同的radC整合位点，并嵌入32 kb的染色体平台中，该平台是欧洲，非洲和亚洲不同来源（患者，健康人类和动物）的菌株共有的。这个平台在数百个粪肠球菌基因组中是保守的，并被提议作为optrA整合的染色体热点。的发现 在不同寄主和国家之间具有共同适应特征和遗传背景的菌株中的optrA表明，在遥远地区发生了共同和独立的遗传事件，这可能解释了optrA阳性菌株容易从头产生。它还预期optrA携带和扩散会急剧增加，这将严重影响利奈唑胺治疗革兰氏阳性感染的功效。