First Report of the Local Spread of Vancomycin-Resistant Enterococci Ascribed to the Interspecies Transmission of a vanA Gene Cluster-Carrying Linear Plasmid
First Report of the Local Spread of Vancomycin-Resistant Enterococci Ascribed to the Interspecies Transmission of a vanA Gene Cluster-Carrying Linear Plasmid
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DOI：
10.1128/msphere.00102-20
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发表时间：
2020-03-01
期刊：
影响因子：
4.8
通讯作者：
Tomita, Haruyoshi
中科院分区：
文献类型：
--
作者：
Hashimoto, Yusuke;Kita, Izumi;Tomita, Haruyoshi
耐万古霉素肠球菌在临床环境中构成威胁，并与世界各地医院的疫情爆发有关。 2017年，日本发生VanA型耐万古霉素肠球菌（VRE）局部传播，从4名住院患者中检出25株肠球菌，其中包括14株屎肠球菌、8株棉子肠球菌和3株卡氏肠球菌。对 VanA 型 VRE 多物种的分子分析揭示了患者之间克隆相关 VRE 菌株的传播以及肠球菌属之间含有 vanA 基因簇的质粒的水平转移。脉冲场凝胶电泳显示未经S1核酸酶处理的质粒DNA能够迁移到凝胶中，表明质粒的拓扑是线性的。全基因组测序显示，该质粒（命名为 pELF2）长 108,102 bp，编码多个抗菌素耐药性基因，包括 ermA 和 ant(9)。推定的复制和转移相关基因的氨基酸序列在 pELF2 和 pELF1 之间高度保守，后者是第一个鉴定的肠球菌接合线性质粒。在比较基因组结构时，pELF2显示出与pELF1相似的主链的存在，特别是两个末端的核苷酸序列，表明其是杂合型线性质粒，具有两个不同的末端结构。 pELF2 具有广泛的宿主范围和肠球菌的高结合频率。 pELF2 可以轻松转移至不同的肠球菌属。体外试验可能解释了多种物种的局部传播，突出了肠球菌线性质粒抗菌素耐药性传播的临床威胁。重要性肠球菌中多药耐药性的增加，包括万古霉素耐药性，是临床环境中的一个主要问题。水平基因转移，例如通过质粒，已被证明在万古霉素耐药性的获得中发挥着至关重要的作用。在万古霉素耐药类型中，VanA型是最常见的一种，由VanA型万古霉素耐药肠球菌（VRE）引起的疫情在世界范围内发生过。在这里，我们描述了一种肠球菌线性质粒，负责 VanA 型 VRE 的多物种局部传播。这样的研究很重要，因为尽管已经报道了由混合肠球菌种类引起的医院暴发，但这种特殊的传播表明质粒跨物种转移。这是一个至关重要的发现，因为抗菌素耐药性传播的高风险需要定期监测和监测。
Vancomycin-resistant enterococci pose a threat in the clinical setting and have been linked to hospital outbreaks worldwide. In 2017, a local spread of VanA-type vancomycin-resistant enterococci (VRE) occurred in Japan, and 25 enterococcal isolates, including 14 Enterococcus faecium, 8 E. raffinosus, and 3 E. casseliflavus isolates, were identified from four inpatients. Molecular analysis of the multispecies of VanA-type VRE revealed the involvement of both the dissemination of clonally related VRE strains between patients and the horizontal transfer of plasmids harboring the vanA gene cluster between Enterococcus spp. Pulsed-field gel electrophoresis showed that the plasmid DNAs without S1 nuclease treatment were able to migrate into the gel, suggesting that the topology of the plasmid was linear. Whole-genome sequencing revealed that this plasmid, designated pELF2, was 108,102 bp long and encoded multiple antimicrobial resistance genes, including ermA and ant(9). The amino acid sequences of putative replication- and transfer-related genes were highly conserved between pELF2 and pELF1, the latter of which was the first identified enterococcal conjugative linear plasmid. On comparing the genomic structure, pELF2 showed the presence of a backbone similar to that of pELF1, especially with respect to the nucleotide sequences of both terminal ends, indicating a hybrid-type linear plasmid, possessing two different terminal structures. pELF2 possessed a broad host range and high conjugation frequencies for enterococci. The easy transfer of pELF2 to different Enterococcus spp. in vitro might explain this local spread of multiple species, highlighting the clinical threat from the spread of antimicrobial resistance by an enterococcal linear plasmid.IMPORTANCE Increasing multidrug resistance, including vancomycin resistance, in enterococci is a major concern in clinical settings. Horizontal gene transfer, such as via plasmids, has been shown to play a crucial role in the acquisition of vancomycin resistance. Among vancomycin resistance types, the VanA type is one of the most prevalent, and outbreaks caused by VanA-type vancomycin-resistant enterococci (VRE) have occurred worldwide. Here, we describe an enterococcal linear plasmid responsible for multispecies local spread of VanA-type VRE. Such a study is important because although hospital outbreaks caused by mixed enterococcal species have been reported, this particular spread indicates plasmid transfer across species. This is a crucial finding because the high risk for such a spread of antimicrobial resistance calls for regular monitoring and surveillance.