STRUCTURE/FUNCTION OF BACTERIAL ADHESION PILI

这项研究的目的是了解的结构和组装 在致病菌上发现粘连菌毛，从而提供洞察力 这些PILI的体系结构如何支持它们作为 毒力因子。细菌的生存和定植需要 细菌附着在宿主上。在许多染色中，这一过程是 由菌毛启动和维持；在引起 肾盂肾炎、粘连和毒力依赖于P-菌毛。Hib-Pili 流感嗜血杆菌表面表达介导人流感病毒 上呼吸道的定殖化，因此它的能力 引起儿童脑膜炎、中耳炎和肺炎等疾病 关于老年人的。随着细菌对传统细菌的抗药性越来越强 抗生素，开发对抗细菌的新疗法是很重要的 感染。有关粘连菌毛的结构信息将提供 为未来合理设计预防细菌的新疗法奠定基础 结合或去除与人类宿主结合的致病细菌。这个 拟议的研究通过结构性研究解决了这一长期目标 细菌黏附菌毛的研究。这些研究主要集中在：1)电子 P-菌毛的显微和三维螺旋重建 玻璃体冰保存和Hib菌毛阴性染色，2)控制 菌毛的损坏/恢复以调查重新形成的可能性 完整的螺旋丝，3)三维结构的研究 P-菌毛与突变型结构蛋白(Pilins)结合，以检测 Papa Pilin是它们组装成紧密缠绕的螺旋结构所必需的 细丝，4)细菌附着试验，以评估 突变和损伤对细菌结合的影响，以及5)体外 由伴侣-毛细蛋白络合物重构杂化毛细管聚合物， 为了提高我们对生物组装过程的理解 典型的大分子。

The aim of this research is to understand the structure and assembly of adhesion pili found on pathogenic bacteria, thereby providing insight into how the architecture of these pili supports their role as a virulence factor. Bacterial survival and colonization require attachment of the bacteria to hosts. In many stains, this process is initiated and maintained by pili; in Escherichia coli that cause pyelonephritis, adhesion and virulence depend on P-pili. Hib-pili expressed on the surface of Haemophilus influenzae mediate H. flu's colonization of the upper respiratory tract, and thus its ability to cause diseases such as childhood meningitis, otitis media, and pneumonia of the elderly. As bacteria become more resistant to traditional antibiotics, it is important to develop new therapies against bacterial infections. Structural information about adhesion pili will provide a basis for future rational design of new therapies to prevent bacterial binding or to remove pathogenic bacteria bound to the human host. The proposed research addresses this long-term goal through structural studies of bacterial adhesion pili. These studies focus on: 1) electron microscopy and three-dimensional (3-D) helical reconstruction of P-pili preserved in vitreous ice and of Hib-pili negative stain, 2) controlled damage/recovery of pili to investigate the possibility of re-formation of intact helical filaments, 3) investigation of the 3-D structure of P-pili with mutant structural proteins (pilins), to examine regions of the PapA pilin essential for their assembly into tightly coiled helical filaments, 4) bacterial attachment assays, to assess the effect of mutations and the effect of damage on bacterial binding, and 5) in vitro reconstitution of hetero-pilin polymers from chaperone-pilin complexes, to improve our understanding of the bioassembly process of a prototypical macromolecule.