Hovius J W, Schuijt T J, de Groot K A, Roelofs J J T H, Oei G A, Marquart J A, de Beer R, van 't Veer C, van der Poll T, Ramamoorthi N, Fikrig E, van Dam A P
Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
J Infect Dis. 2008 Oct 15;198(8):1189-97. doi: 10.1086/591917.
Ixodes ticks are the main vectors for Borrelia burgdorferi sensu lato. In the United States, B. burgdorferi is the sole causative agent of Lyme borreliosis and is transmitted by Ixodes scapularis. In Europe, 3 Borrelia species-B. burgdorferi, B. garinii, and B. afzelii-are prevalent, which are transmitted by Ixodes ricinus. The I. scapularis salivary protein Salp15 has been shown to bind to B. burgdorferi outer surface protein (Osp) C, protecting the spirochete from antibody-mediated killing.
We recently identified a Salp15 homologue in I. ricinus, Salp15 Iric-1. Here, we have demonstrated, by solid-phase overlays, enzyme-linked immunosorbent assay, and surface plasmon resonance, that Salp15 Iric-1 binds to B. burgdorferi OspC. Importantly, this binding protected the spirochete from antibody-mediated killing in vitro and in vivo; immune mice rechallenged with B. burgdorferi preincubated with Salp15 Iric-1 displayed significantly higher Borrelia numbers and more severe carditis, compared with control mice. Furthermore, Salp15 Iric-1 was capable of binding to OspC from B. garinii and B. afzelii, but these Borrelia species were not protected from antibody-mediated killing.
Salp15 Iric-1 interacts with all European Borrelia species but differentially protects B. burgdorferi from antibody-mediated killing, putatively giving this Borrelia species a survival advantage in nature.
硬蜱是伯氏疏螺旋体狭义种的主要传播媒介。在美国,伯氏疏螺旋体是莱姆病的唯一病原体,由肩突硬蜱传播。在欧洲,3种伯氏疏螺旋体——伯氏疏螺旋体、伽氏疏螺旋体和阿氏疏螺旋体——较为常见,由蓖麻硬蜱传播。已证明肩突硬蜱唾液蛋白Salp15可与伯氏疏螺旋体外膜蛋白(Osp)C结合,保护螺旋体免受抗体介导的杀伤。
我们最近在蓖麻硬蜱中鉴定出一种Salp15同源物,即Salp15 Iric-1。在此,我们通过固相覆盖法、酶联免疫吸附测定和表面等离子体共振证明,Salp15 Iric-1可与伯氏疏螺旋体OspC结合。重要的是,这种结合在体外和体内均保护螺旋体免受抗体介导的杀伤;与对照小鼠相比,用与Salp15 Iric-1预孵育的伯氏疏螺旋体再次攻击的免疫小鼠体内的伯氏疏螺旋体数量显著更高,且心脏炎更严重。此外,Salp15 Iric-1能够与伽氏疏螺旋体和阿氏疏螺旋体的OspC结合,但这些伯氏疏螺旋体物种未免受抗体介导的杀伤。
Salp15 Iric-1与所有欧洲伯氏疏螺旋体物种相互作用,但对伯氏疏螺旋体免受抗体介导的杀伤具有不同的保护作用,推测这赋予了该伯氏疏螺旋体物种在自然环境中的生存优势。