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万古霉素耐药粪肠球菌在澳大利亚的变迁格局:基于人群水平的基因组研究。

The changing landscape of vancomycin-resistant Enterococcus faecium in Australia: a population-level genomic study.

机构信息

The Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, The University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, 792 Elizabeth Street, Level 1, Melbourne, Victoria, Australia.

Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, 677 Huntington Avenue, Level 5, Boston, MA, USA.

出版信息

J Antimicrob Chemother. 2018 Dec 1;73(12):3268-3278. doi: 10.1093/jac/dky331.

Abstract

BACKGROUND

Vancomycin-resistant Enterococcus faecium (VREfm) represent a major source of nosocomial infection worldwide. In Australia, there has been a recent concerning increase in bacteraemia associated with the vanA genotype, prompting investigation into the genomic epidemiology of VREfm.

METHODS

A population-level study of VREfm (10 November-9 December 2015) was conducted. A total of 321 VREfm isolates (from 286 patients) across Victoria State were collected and sequenced with Illumina NextSeq. SNPs were used to assess relatedness. STs and genes associated with resistance and virulence were identified. The vanA-harbouring plasmid from an isolate from each ST was assembled using long-read data. Illumina reads from remaining isolates were then mapped to these assemblies to identify their probable vanA-harbouring plasmid.

RESULTS

vanA-VREfm comprised 17.8% of isolates. ST203, ST80 and a pstS(-) clade, ST1421, predominated (30.5%, 30.5% and 37.2%, respectively). Most vanB-VREfm were ST796 (77.7%). vanA-VREfm were more closely related within hospitals versus between them [core SNPs 10 (IQR 1-357) versus 356 (179-416), respectively], suggesting discrete introductions of vanA-VREfm, with subsequent intra-hospital transmission. In contrast, vanB-VREfm had similar core SNP distributions within versus between hospitals, due to widespread dissemination of ST796. Different vanA-harbouring plasmids were found across STs. With the exception of ST78 and ST796, Tn1546 transposons also varied. Phylogenetic analysis revealed Australian strains were often interspersed with those from other countries, suggesting ongoing cross-continental transmission.

CONCLUSIONS

Emerging vanA-VREfm in Australia is polyclonal, indicating repeat introductions of vanA-VREfm into hospitals and subsequent dissemination. The close relationship to global strains reinforces the need for ongoing screening and control of VREfm in Australia and abroad.

摘要

背景

耐万古霉素粪肠球菌(VREfm)是全球医院感染的主要来源。在澳大利亚,与 vanA 基因型相关的菌血症近期令人担忧地增加,促使人们对 VREfm 的基因组流行病学进行调查。

方法

对 VREfm(2015 年 11 月 10 日至 12 月 9 日)进行了一项人群水平的研究。在维多利亚州共采集了 321 株 VREfm 分离株(来自 286 名患者),并使用 Illumina NextSeq 进行测序。单核苷酸多态性用于评估相关性。确定了与耐药性和毒力相关的 ST 和基因。使用长读数据组装来自每个 ST 的分离株中携带 vanA 的质粒。然后,将 Illumina 读取映射到这些组装体上,以鉴定其可能携带 vanA 的质粒。

结果

vanA-VREfm 占分离株的 17.8%。ST203、ST80 和 pstS(-) 分支,ST1421 占主导地位(分别为 30.5%、30.5%和 37.2%)。大多数 vanB-VREfm 为 ST796(77.7%)。vanA-VREfm 在医院内的相关性比在医院之间更密切[核心 SNP 为 10(IQR 1-357)与 356(179-416)],表明 vanA-VREfm 是离散引入的,随后在医院内传播。相比之下,vanB-VREfm 在医院内和医院之间具有相似的核心 SNP 分布,这是由于 ST796 的广泛传播。不同的 vanA 携带质粒在 ST 之间有所不同。除了 ST78 和 ST796 之外,Tn1546 转座子也有所不同。系统发育分析显示,澳大利亚菌株经常与其他国家的菌株交织在一起,表明跨大陆的传播仍在继续。

结论

澳大利亚新出现的 vanA-VREfm 呈多克隆性,表明 vanA-VREfm 反复引入医院并随后传播。与全球菌株的密切关系强化了在澳大利亚和国外持续筛查和控制 VREfm 的必要性。

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