Hellwage J, Meri T, Heikkilä T, Alitalo A, Panelius J, Lahdenne P, Seppälä I J, Meri S
Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Haartmaninkatu 3, FIN-00014 Helsinki, Finland.
J Biol Chem. 2001 Mar 16;276(11):8427-35. doi: 10.1074/jbc.M007994200. Epub 2000 Dec 11.
Spirochete bacteria of the Borrelia burgdorferi sensu lato complex cause Lyme borreliosis. The three pathogenic subspecies Borrelia garinii, Borrelia afzelii, and Borrelia burgdorferi sensu stricto differ in their disease profiles and susceptibility to complement lysis. We investigated whether complement resistance of Borreliae could be due to acquisition of the main soluble inhibitors of the alternative complement pathway, factor H and the factor H-like protein 1. When exposed to nonimmune EDTA-plasma, the serum-resistant B. afzelii and B. burgdorferi sensu stricto strains bound factor H/factor H-like protein 1 to their surfaces. Assays with radiolabeled proteins showed that factor H bound strongly to the B. burgdorferi sensu stricto strain. To identify factor H ligands on the borrelial surface, we analyzed a panel of outer surface proteins of B. burgdorferi sensu stricto with the surface plasmon resonance technique. The outer surface lipoprotein OspE was identified as a specific ligand for factor H. Using recombinant constructs of factor H, the binding site for OspE was localized to the C-terminal short consensus repeat domains 15-20. Specific binding of factor H to B. burgdorferi sensu stricto OspE may help the pathogen to evade complement attack and phagocytosis.
狭义伯氏疏螺旋体复合群的螺旋体细菌可引起莱姆病。三种致病性亚种，即伽氏疏螺旋体、阿氏疏螺旋体和狭义伯氏疏螺旋体，在疾病谱和对补体溶解的敏感性方面存在差异。我们研究了疏螺旋体对补体的抗性是否可能归因于获得了替代补体途径的主要可溶性抑制剂——因子H和因子H样蛋白1。当暴露于非免疫EDTA血浆时，血清抗性的阿氏疏螺旋体和狭义伯氏疏螺旋体菌株将因子H/因子H样蛋白1结合到其表面。用放射性标记蛋白进行的分析表明，因子H与狭义伯氏疏螺旋体菌株强烈结合。为了鉴定疏螺旋体表面的因子H配体，我们用表面等离子体共振技术分析了狭义伯氏疏螺旋体的一组外表面蛋白。外表面脂蛋白OspE被鉴定为因子H的特异性配体。使用因子H的重组构建体，OspE的结合位点定位于C末端短共有重复结构域15 - 20。因子H与狭义伯氏疏螺旋体OspE的特异性结合可能有助于病原体逃避补体攻击和吞噬作用。
