Endocarditis and biofilm-associated pili of Enterococcus faecalis
Endocarditis and biofilm-associated pili of Enterococcus faecalis
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DOI：
10.1172/jci29021
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发表时间：
2006-10-01
影响因子：
15.9
通讯作者：
Murray, Barbara E.
中科院分区：
文献类型：
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作者：
Nallapareddy, Sreedhar R.;Singh, Kavindra V.;Murray, Barbara E.
粪肠球菌（Enterococcus faecalis）是细菌性心内膜炎的院内机会主义者和常见原因，其多重耐药性的增加强调了对替代治疗方法（如免疫治疗或免疫预防）的需求。在早期的研究中，我们证明了E.粪心内膜炎患者血清与重组形式的9 E.粪肠球菌细胞壁锚定蛋白;其中，我们现在已经表征了3个基因的体内表达位点和相关的分选酶基因（编码分选酶C; SrtC）。在这里，我们通过突变分析和互补，证明了Ebp（编码心内膜炎和生物膜相关皮利）操纵子和srtC对E.粪肠球菌菌株OG 1 RF。此外，使用抗EbpA-EbpC蛋白的抗血清以及患者血清的免疫金电子显微镜证实E.粪便产生多形性表面皮利。Pill的组装及其细胞壁附着似乎通过指定SrtC交联Ebp蛋白的机制发生。重要的是，在心内膜炎模型中，无纤毛的等位基因置换突变体显著减弱。这些生物学上重要的表面皮利在人类心内膜炎时具有抗原性，由普遍存在的E. faecalis操纵子，可能是一个有用的免疫靶点，旨在预防和/或治疗这种病原体的研究。
Increasing multidrug resistance in Enterococcus faecalis, a nosocomial opportunist and common cause of bacterial endocarditis, emphasizes the need for alternative therapeutic approaches such as immunotherapy or immunoprophylaxis. In an earlier study, we demonstrated the presence of antibodies in E. faecalis endocarditis patient sera to recombinant forms of 9 E. faecalis cell wall-anchored proteins; of these, we have now characterized an in vivo-expressed locus of 3 genes and an associated sortase gene (encoding sortase C; SrtC). Here, using mutation analyses and complementation, we demonstrated that both the ebp (encoding endocarditis and biofilm-associated pili) operon and srtC are important for biofilm production of E. faecalis strain OG1RF. In addition, immunogold electron microscopy using antisera against EbpA-EbpC proteins as well as patient serum demonstrated that E. faecalis produces pleomorphic surface pili. Assembly of pill and their cell wall attachment appeared to occur via a mechanism of cross-linking of the Ebp proteins by the designated SrtC. Importantly, a nonpiliated, allelic replacement mutant was significantly attenuated in an endocarditis model. These biologically important surface pili, which are antigenic in humans during endocarditis and encoded by a ubiquitous E. faecalis operon, may be a useful immunotarget for studies aimed at prevention and/or treatment of this pathogen.