MOLECULAR BASIS OF PILUS-MEDIATED GONOCOCCAL ADHESION

项目总结 淋球菌(GC)是一个日益严重的公共卫生问题，由于不断增加的 抗生素耐药性和缺乏疫苗。已知IV型菌毛(TFP)对GC毒力是必不可少的 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。然而， 负责高亲和力黏附的特异性GC蛋白(S)和宿主受体(S)的身份尚不清楚 为人所知。二十年的公开实验有力地支持了这一假设，即低丰度蛋白质 PILC是GC TFP提出的一种高亲和力粘附素。然而，人们对其整体结构知之甚少。 PILC，它与TFP结合的机制，以及它可能参与的宿主受体。 在本项目中，我们将使用体内遗传测试和体外生化分析来测试PILC模型 职能组织，我们将使用所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PILC与菌毛的结合机制，PILC影响菌毛的机制 生物发生，以及GC和密切相关的病原体脑膜炎奈瑟氏菌附着的机制 人体上皮组织开始感染。

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.