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全基因组筛选鉴定出磷酸转移酶系统通透酶 BepA 参与粪肠球菌心内膜炎和生物膜形成。

Genome-wide Screening Identifies Phosphotransferase System Permease BepA to Be Involved in Enterococcus faecium Endocarditis and Biofilm Formation.

机构信息

Department of Medical Microbiology, University Medical Center Utrecht, The Netherlands.

Division of Pediatric Infectious Diseases, Hauner Children's Hospital, Ludwigs-Maximilian Universität München Center for Infectious Disease and Travel Medicine, University Medical Center Freiburg, Germany.

出版信息

J Infect Dis. 2016 Jul 15;214(2):189-95. doi: 10.1093/infdis/jiw108. Epub 2016 Mar 16.

DOI:10.1093/infdis/jiw108
PMID:26984142
Abstract

Enterococcus faecium is a common cause of nosocomial infections, of which infective endocarditis is associated with substantial mortality. In this study, we used a microarray-based transposon mapping (M-TraM) approach to evaluate a rat endocarditis model and identified a gene, originally annotated as "fruA" and renamed "bepA," putatively encoding a carbohydrate phosphotransferase system (PTS) permease (biofilm and endocarditis-associated permease A [BepA]), as important in infective endocarditis. This gene is highly enriched in E. faecium clinical isolates and absent in commensal isolates that are not associated with infection. Confirmation of the phenotype was established in a competition experiment of wild-type and a markerless bepA mutant in a rat endocarditis model. In addition, deletion of bepA impaired biofilm formation in vitro in the presence of 100% human serum and metabolism of β-methyl-D-glucoside. β-glucoside metabolism has been linked to the metabolism of glycosaminoglycans that are exposed on injured heart valves, where bacteria attach and form vegetations. Therefore, we propose that the PTS permease BepA is directly implicated in E. faecium pathogenesis.

摘要

屎肠球菌是一种常见的医院获得性感染病原体,其中感染性心内膜炎与较高的死亡率相关。在本研究中,我们使用基于微阵列的转座子图谱(M-TraM)方法评估大鼠心内膜炎模型,鉴定出一个基因,最初被注释为“fruA”,并重新命名为“bepA”,推测其编码碳水化合物磷酸转移酶系统(PTS)通透酶(生物膜和心内膜炎相关通透酶 A [BepA]),在感染性心内膜炎中起重要作用。该基因在屎肠球菌临床分离株中高度富集,而在不与感染相关的共生分离株中不存在。在大鼠心内膜炎模型中,通过野生型和无标记 bepA 突变体的竞争实验,对表型进行了确认。此外,在存在 100%人血清的情况下,bepA 的缺失会损害体外生物膜的形成以及β-甲基-D-葡萄糖苷的代谢。β-葡糖苷代谢与暴露于受损心瓣膜上的糖胺聚糖的代谢有关,细菌附着并形成赘生物。因此,我们提出 PTS 通透酶 BepA 直接参与屎肠球菌的发病机制。

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