Schools of Cellular & Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.
Mol Microbiol. 2011 Dec;82(5):1129-49. doi: 10.1111/j.1365-2958.2011.07876.x. Epub 2011 Nov 4.
Complement evasion is an important survival strategy of Neisseria meningitidis (Nm) during colonization and infection. Previously, we have shown that Nm Opc binds to serum vitronectin to inhibit complement-mediated killing. In this study, we demonstrate meningococcal interactions with vitronectin via a novel adhesin, Msf (meningococcal surface fibril, previously NhhA or Hsf). As with Opc, Msf binds preferentially to activated vitronectin (aVn), engaging at its N-terminal region but the C-terminal heparin binding domain may also participate. However, unlike Opc, the latter binding is not heparin-mediated. By binding to aVn, Msf or Opc can impart serum resistance, which is further increased in coexpressers, a phenomenon dependent on serum aVn concentrations. The survival fitness of aVn-binding derivatives was evident from mixed population studies, in which msf/opc mutants were preferentially depleted. In addition, using vitronectin peptides to block Msf-aVn interactions, aVn-induced inhibition of lytic C5b-9 formation and of serum killing could be reversed. As Msf-encoding gene is ubiquitous in the meningococcal strains examined and is expressed in vivo, serum resistance via Msf may be of significance to meningococcal pathogenesis. The data imply that vitronectin binding may be an important strategy for the in vivo survival of Nm for which the bacterium has evolved redundant mechanisms.
补体逃避是脑膜炎奈瑟菌（Nm）在定植和感染期间的重要生存策略。先前，我们已经表明 Nm Opc 结合血清 vitronectin 以抑制补体介导的杀伤。在这项研究中，我们通过一种新型黏附素 Msf（脑膜炎球菌表面纤丝，先前称为 NhhA 或 Hsf）证明脑膜炎球菌与 vitronectin 的相互作用。与 Opc 一样，Msf 优先与激活的 vitronectin（aVn）结合，结合于其 N 端区域，但 C 端肝素结合结构域也可能参与。然而，与 Opc 不同，后者的结合不是肝素介导的。通过与 aVn 结合，Msf 或 Opc 可以赋予血清抗性，在共表达体中进一步增加，这种现象依赖于血清 aVn 浓度。从混合群体研究中可以明显看出 aVn 结合衍生物的生存适应性，其中 msf/opc 突变体被优先耗尽。此外，使用 vitronectin 肽阻断 Msf-aVn 相互作用，可以逆转 aVn 诱导的裂解 C5b-9 形成和血清杀伤的抑制。由于在研究的脑膜炎球菌菌株中普遍存在编码 Msf 的基因，并在体内表达，因此通过 Msf 实现的血清抗性可能对脑膜炎球菌发病机制具有重要意义。数据表明，vitronectin 结合可能是 Nm 体内生存的重要策略，细菌已经进化出冗余机制。
