MOLECULAR BASIS OF PILUS-MEDIATED GONOCOCCAL ADHESION

项目摘要 淋病奈瑟菌（GC）是一个日益严重的公共卫生问题，由于越来越多的人感染， 抗生素耐药性和缺乏疫苗。IV型皮利（Tfp）是GC毒力所必需的， 有强有力的证据表明，Tfp与人类细胞上的高亲和力受体结合。但 负责高亲和性粘附的特异性GC蛋白和宿主受体的身份并不 知道的20年来发表的实验有力地支持了这样一种假设，即低丰度蛋白质 PilC是由GC Tfp呈递的高亲和力粘附素。然而，人们对它的整体结构知之甚少。 PilC，它与Tfp相关的机制，以及它可能参与的宿主受体。 在本研究中，我们将使用体内遗传学测试和体外生化分析来测试PilC模型 我们将使用由此产生的信息和试剂来开始 鉴定人粘膜上皮细胞上的高亲和力受体。该项目的影响将包括 阐明了PilC与皮利结合的机制、PilC影响菌毛的机制 生物发生，以及GC和密切相关的病原体N.脑膜炎粘附于 人类上皮组织引发感染。

PROJECT SUMMARY Neisseria gonorrhoeae (GC) is a growing public health problem which is likely to worsen due to increasing antibiotic resitance and the lack of a vaccine. Type IV pili (Tfp) are known to be essential for GC virulence in humans, and there is strong evidence that Tfp bind to high-affinity receptors on human cells. However, the identities of both the specific GC protein(s) and host receptor(s) responsible for high-affinity adherence are not known. Twenty years of pubished experiments strongly support the hypothesis that the low-abundance protein PilC is the high-affinity adhesin presented by GC Tfp. However, little is known about the overall structure of PilC, the mechanisms through which it associates with Tfp, and the host receptors that it presumably engages. In this project we will use in vivo genetic tests and in vitro biochemical analyses to test models of PilC functional organization, and we will use the resulting information and reagents to begin the process of identifying high-affinity receptors on human mucosal epithelial cells. The impacts of this project will include clarifying the mechanisms of PilC association with pili, the mechanisms through which PilC influences pilus biogenesis, and the mechanisms through which GC and the closely related pathogen N. meningitidis adhere to human epithelial tissues to initiate infection.