Identification and characterization of a linear-plasmid-encoded factor H-binding protein (FhbA) of the relapsing fever Spirochete Borrelia hermsii

Identification and characterization of a linear-plasmid-encoded factor H-binding protein (FhbA) of the relapsing fever Spirochete Borrelia hermsii
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DOI:
10.1128/jb.186.9.2612-2618.2004
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发表时间:
2004-05-01
影响因子:
3.2
通讯作者:
Marconi, RT
Marconi, RT
中科院分区:
生物学3区
文献类型:
--
作者:
Hovis, KM;McDowell, JV;Marconi, RT

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在北美,蜱传回归热(TBRF)是由螺旋体物种Borrelia hermsii,Borrelia parkeri和Borrelia turicularis引起的。我们以前证明,一些分离的B。hermsii和B. parkeri能够结合因子H,并且细胞结合因子H可以参与因子I介导的C3b裂解。结合因子H的分离株表达因子H结合蛋白(FHBP),我们估计其大小约为19至20 kDa,因此,在进一步表征之前,暂时命名为FHBP19。在本报告之前,还没有TBRF螺旋体的FHBPs的特征。在这里,我们已经恢复了编码B的FHBP的基因。hermsii YOR,并测定其序列。该基因编码22.7 kDa的全长蛋白质,经处理后预测为20.5 kDa。这种蛋白质,我们重新命名为因子H结合蛋白A(FhbA),是B所特有的。赫姆斯。双向脉冲场凝胶电泳和杂交分析表明,B。编码FhbA的hermsii基因是定位到约220kb的线性质粒的单个遗传基因座。还评估了FhbA的一般性质。发现蛋白质是表面暴露和脂化的。在感染小鼠中对FhbA的抗体应答的分析揭示,它在感染期间是抗原性的,表明在感染期间表达。FhbA的鉴定和表征为进一步了解回归热螺旋体致病的分子机制提供了依据。
In North America, tick-borne relapsing fever (TBRF) is caused by the spirochete species Borrelia hermsii, Borrelia parkeri, and Borrelia turicatae. We previously demonstrated that some isolates of B. hermsii and B. parkeri are capable of binding factor H and that cell-bound factor H can participate in the factor I-mediated cleavage of C3b. Isolates that bound factor H expressed a factor H-binding protein (FHBP) that we estimated to be approximately 19 to 20 kDa in size and thus, pending further characterization, temporarily designated FHBP19. Until this report, none of the FHBPs of the TBRF spirochetes had been characterized. Here we have recovered the gene encoding the FHBP of B. hermsii YOR from a lambda ZAP II library and determined its sequence. The gene encodes a full-length protein of 22.7 kDa, which after processing is predicted to be 20.5 kDa. This protein, which we redesignate factor H-binding protein A (FhbA), is unique to B. hermsii. Two-dimensional pulsed-field gel electrophoresis and hybridization analyses revealed that the B. hermsii gene encoding FhbA is a single genetic locus that maps to a linear plasmid of approximately 220 kb. The general properties of FhbA were also assessed. The protein was found to be surface exposed and lipidated. Analysis of the antibody response to FhbA in infected mice revealed that it is antigenic during infection, indicating expression during infection. The identification and characterization of FhbA provides further insight into the molecular mechanisms of pathogenesis of the relapsing fever spirochetes.