Alitalo Antti, Meri Taru, Comstedt Pär, Jeffery Luke, Tornberg Johanna, Strandin Tomas, Lankinen Hilkka, Bergström Sven, Cinco Marina, Vuppala Santosh R, Akins Darrin R, Meri Seppo
Department of Bacteriology and Immunology, Haartman Institute and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
Eur J Immunol. 2005 Oct;35(10):3043-53. doi: 10.1002/eji.200526354.
The Lyme disease-pathogen Borrelia burgdorferi binds the complement inhibitor factor H (FH) to its outer surface protein E- (OspE) and BbA68-families of lipoproteins. In earlier studies, only serum-resistant strains of the genospecies B. burgdorferi sensu stricto or B. afzelii, but not serum-sensitive B. garinii strains, have been shown to bind FH. Since B. garinii often causes neuroborreliosis in man, we have readdressed the interactions of B. garinii with FH. B. garinii 50/97 strain did not express FH-binding proteins. By transforming the B. garinii 50/97 strain with an OspE-encoding gene from complement-resistant B. burgdorferi (ospE-297), its resistance to serum killing could be increased. OspE genes were detected and cloned from the B. garinii BITS, Pistoia and 40/97 strains by PCR and sequencing. The deduced amino acid sequences differed in an N-terminal lysine-rich FH-binding region from OspE sequences of resistant strains. Recombinant B. garinii BITS OspE protein was found to have a considerably lower FH-binding activity than the B. burgdorferi sensu stricto 297 OspE protein P21 (P21-297). Unlike bacteria that had been kept in culture for a long time, neurovirulent B. garinii strains from neuroborreliosis patients were found to express approximately 27-kDa FH-binding proteins. These were not recognized by polyclonal anti-OspE or anti-BbA68 antibodies. We conclude that B. garinii strains carry ospE genes but have a decreased expression of OspE proteins and a reduced ability to bind FH, especially when grown for prolonged periods in vitro. Recently isolated neuroinvasive B. garinii strains, however, can express FH-binding proteins, which may contribute to the virulence of neuroborreliosis-causing B. garinii strains.
莱姆病病原体伯氏疏螺旋体（Borrelia burgdorferi）将补体抑制剂因子H（FH）与其外表面蛋白E（OspE）和脂蛋白BbA68家族结合。在早期研究中，仅狭义伯氏疏螺旋体或阿氏疏螺旋体的血清抗性菌株能结合FH，而血清敏感的伽氏疏螺旋体菌株则不能。由于伽氏疏螺旋体常导致人类神经莱姆病，我们重新研究了伽氏疏螺旋体与FH的相互作用。伽氏疏螺旋体50/97菌株不表达FH结合蛋白。通过用来自补体抗性伯氏疏螺旋体的OspE编码基因（ospE - 297）转化伽氏疏螺旋体50/97菌株，其对血清杀伤的抗性得以增强。通过PCR和测序从伽氏疏螺旋体BITS、皮斯托亚和40/97菌株中检测并克隆了OspE基因。推导的氨基酸序列在富含N端赖氨酸的FH结合区域与抗性菌株的OspE序列不同。发现重组伽氏疏螺旋体BITS OspE蛋白的FH结合活性比狭义伯氏疏螺旋体297 OspE蛋白P21（P21 - 297）低得多。与长期培养的细菌不同，发现来自神经莱姆病患者的神经毒性伽氏疏螺旋体菌株表达约27 kDa的FH结合蛋白。这些蛋白不被多克隆抗OspE或抗BbA68抗体识别。我们得出结论，伽氏疏螺旋体菌株携带ospE基因，但OspE蛋白表达降低且结合FH的能力减弱，尤其是在体外长时间培养时。然而，最近分离出的神经侵袭性伽氏疏螺旋体菌株可表达FH结合蛋白，这可能有助于导致神经莱姆病的伽氏疏螺旋体菌株的毒力。
