Linezolid resistance in clinical isolates of Staphylococcus epidermidis from German hospitals and characterization of two cfr-carrying plasmids
Linezolid resistance in clinical isolates of Staphylococcus epidermidis from German hospitals and characterization of two cfr-carrying plasmids
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DOI：
10.1093/jac/dkv025
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发表时间：
2015-06-01
影响因子：
5.2
通讯作者：
Layer, Franziska
中科院分区：
文献类型：
--
作者：
Bender, Jennifer;Strommenger, Birgit;Layer, Franziska
目的：本研究是一个详细的调查表皮葡萄球菌临床分离株表现出利奈唑胺耐药。分析了来自八家德国医院的表皮葡萄球菌，包括来自2012年1月至2013年4月期间疑似医院相关爆发的分离株，关于它们的抗菌药物敏感性和23 S rRNA、rplC、rplD和rplV基因中cfr和/或突变的存在。通过MLST和SmaI宏观限制性分析估计分离株的相关性。通过Illumina测序进行CFR质粒的表征。结果：利奈唑胺的MIC在分离株之间差异很大。在耐药水平、cfr和核糖体靶位点突变之间没有发现明显的相关性。S.来自两家医院的表皮分离物被证实为克隆相关的，表明各自的克隆在1年的时间内传播。下一代测序揭示了两种不同类型的cfr表达质粒，它们在遗传排列和组成上都与先前发表的cfr质粒不同：p12-00322样质粒显示cfr掺入pGO 1样骨架中，并显示出种内和种间接合转移的能力。在德国很少从人临床来源中分离出表皮葡萄球菌。在这里，我们描述了这些菌株的出现和爆发。我们检测到以前描述的和新的点突变的23 S核糖体基因。cfr基因仅存在于6个分离株中。然而，这是第一个已知的cfr掺入接合载体的描述;在选择压力下，这些载体可能会引起合理的关注。
Objectives: This study was a detailed investigation of Staphylococcus epidermidis clinical isolates exhibiting linezolid resistance.Methods: Thirty-six linezolid-resistant S. epidermidis from eight German hospitals, including isolates from suspected hospital-associated outbreaks between January 2012 and April 2013, were analysed with respect to their antimicrobial susceptibility and the presence of cfr and/or mutations in the 23S rRNA, rplC, rplD and rplV genes. Relatedness of isolates was estimated by MLST and SmaI macrorestriction analysis. Characterization of cfr plasmids was carried out by means of Illumina sequencing.Results: The MICs of linezolid varied substantially between the isolates. No apparent correlation was detected between the level of resistance, the presence of cfr and ribosomal target site mutations. S. epidermidis isolates from two hospitals were confirmed as clonally related, indicating the spread of the respective clone over a period of 1 year. Next-generation sequencing revealed two different categories of cfr-expressing plasmids, both of them varying in genetic arrangement and composition from previously published cfr plasmids: p12-00322-like plasmids showed incorporation of cfr into a pGO1-like backbone and displayed capabilities for intra-and inter-species conjugational transfer.Conclusions: To date, linezolid-resistant S. epidermidis have rarely been isolated from human clinical sources in Germany. Here, we describe the emergence and outbreaks of these strains. We detected previously described and novel point mutations in the 23S ribosomal genes. The cfr gene was only present in six isolates. However, this is the first known description of cfr incorporation into conjugative vectors; under selective pressure, these vectors could give reasonable cause for concern.