Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Frankfurt, Germany.
PLoS One. 2013;8(1):e53659. doi: 10.1371/journal.pone.0053659. Epub 2013 Jan 8.
Spirochetes belonging to the Borrelia (B.) burgdorferi sensu lato complex differ in their resistance to complement-mediated killing, particularly in regard to human serum. In the present study, we elucidate the serum and complement susceptibility of B. valaisiana, a genospecies with the potential to cause Lyme disease in Europe as well as in Asia. Among the investigated isolates, growth of ZWU3 Ny3 was not affected while growth of VS116 and Bv9 was strongly inhibited in the presence of 50% human serum. Analyzing complement activation, complement components C3, C4 and C6 were deposited on the surface of isolates VS116 and Bv9, and similarly the membrane attack complex was formed on their surface. In contrast, no surface-deposited components and no aberrations in cell morphology were detected for serum-resistant ZWU3 Ny3. While further investigating the protective role of bound complement regulators in mediating complement resistance, we discovered that none of the B. valaisiana isolates analyzed bound complement regulators Factor H, Factor H-like protein 1, C4b binding protein or C1 esterase inhibitor. In addition, B. valaisiana also lacked intrinsic proteolytic activity to degrade complement components C3, C3b, C4, C4b, and C5. Taken together, these findings suggest that certain B. valaisiana isolates differ in their capability to resist complement-mediating killing by human serum. The molecular mechanism utilized by B. valaisiana to inhibit bacteriolysis appears not to involve binding of the key host complement regulators of the alternative, classical, and lectin pathways as already known for serum-resistant Lyme disease or relapsing fever borreliae.
螺旋体属于伯氏疏螺旋体(B.)burgdorferi 广义复合种,其对补体介导杀伤的抵抗力不同,特别是在人血清方面。在本研究中,我们阐明了 B. valaisiana 的血清和补体敏感性,B. valaisiana 是一种具有在欧洲和亚洲引起莱姆病潜力的种。在所研究的分离株中,ZUW3 Ny3 的生长不受影响,而 VS116 和 Bv9 的生长在存在 50%人血清时受到强烈抑制。分析补体激活,发现补体成分 C3、C4 和 C6 沉积在 VS116 和 Bv9 的表面上,同样在其表面形成膜攻击复合物。相比之下,血清抗性 ZWU3 Ny3 未检测到表面沉积的成分和细胞形态异常。在进一步研究结合补体调节剂在介导补体抗性中的保护作用时,我们发现分析的 B. valaisiana 分离株均未结合补体调节剂因子 H、因子 H 样蛋白 1、C4b 结合蛋白或 C1 酯酶抑制剂。此外,B. valaisiana 也缺乏内在的蛋白水解活性来降解补体成分 C3、C3b、C4、C4b 和 C5。综上所述,这些发现表明某些 B. valaisiana 分离株在抵抗人血清介导的杀伤方面存在差异。B. valaisiana 抑制细菌溶解的分子机制似乎不涉及已为人所知的耐血清莱姆病或回归热螺旋体的替代、经典和凝集素途径的关键宿主补体调节剂的结合。