Sequence-Based Epidemiology of an OXA-48 Plasmid during Hospital Outbreak
Sequence-Based Epidemiology of an OXA-48 Plasmid during Hospital Outbreak
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DOI：
10.1128/aac.01204-19
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发表时间：
2019-12-01
影响因子：
4.9
通讯作者：
Fluit, Ad C.
中科院分区：
文献类型：
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作者：
Hidalgo, Laura;de Been, Mark;Fluit, Ad C.
在荷兰发生的一次大规模OXA-48疫情中，产OXA-48肠杆菌科在至少118名患者中传播，表明这种耐药基因通过一种或多种质粒进行水平转移。阐明耐药质粒的传播动力学受到经典分型方法分辨率低的阻碍。本研究旨在使用新一代测序方法研究携带OXA-48碳青霉烯酶的质粒的分子流行病学。共选择了从医院爆发中收集的68株产OXA-48肠杆菌科分离株，以及来自荷兰、利比亚和土耳其的22株非爆发相关的产OXA-48肠杆菌科分离株。使用Illumina MiSeq平台对质粒进行测序，并组装和分析读取集。在所有质粒中，bla（OXA-48）包埋在转座子Tn1999.2中并定位在ca. 14个种属的62-kb IncL/M接合质粒。所有质粒的核心序列比对之间最多有2个单核苷酸多态性（SNP）。在荷兰和其他国家的非爆发分离株中检测到该质粒的密切相关序列变体。在89株产OXA-48的分离株中，有31株还携带bla（CTX-M-15），其不位于携带bla（OXA-48）的质粒上。对携带bla（CTX-M-15）的四种质粒的测序揭示了广泛的质粒异质性。一约62-kb质粒是导致荷兰一家医院爆发OXA-48的原因。我们的研究结果提供了强有力的证据，在医院爆发期间，基于质粒的OXA-48在宿主种间和宿主间传播。这些研究结果证实了产碳青霉烯酶肠杆菌科（CPE）的复杂流行病学。
A large OXA-48 outbreak in The Netherlands involved the spread of OXA-48-producing Enterobacteriaceae among at least 118 patients, suggesting horizontal transfer of this resistance gene through one or more plasmids. Elucidating transmission dynamics of resistance plasmids is hampered by the low resolution of classic typing methods. This study aimed to investigate the molecular epidemiology of plasmids carrying the OXA-48 carbapenemase using a next-generation sequencing approach. A total of 68 OXA-48-producing Enterobacteriaceae isolates collected from the hospital outbreak, as well as 22 non-outbreak-related OXA-48-producing Enterobacteriaceae isolates from The Netherlands, Libya, and Turkey were selected. Plasmids were sequenced using the Illumina MiSeq platform, and read sets were assembled and analyzed. In all plasmids, bla(OXA-48) was embedded in transposon Tn1999.2 and located on a ca. 62-kb IncL/M conjugative plasmid in 14 different species. There were a maximum of 2 single nucleotide polymorphisms (SNPs) between the core sequence alignment of all plasmids. Closely related sequence variants of this plasmid were detected in nonout-break isolates from The Netherlands and other countries. Thirty-one of 89 OXA-48-producing isolates also harbored bla(CTX-M-15, )which was not located on the bla(OXA-48)-carrying plasmid. Sequencing of four plasmids harboring bla(CTX-M-15) revealed extensive plasmid heterogeneity. A ca. 62-kb plasmid was responsible for the OXA-48 outbreak in a Dutch hospital. Our findings provide strong evidence for both within-host interspecies and between-host dissemination of plasmid-based OXA-48 during a nosocomial outbreak These findings exemplify the complex epidemiology of carbapenemase-producing Enterobacteriaceae (CPE).