Mechanisms of Gonococcal Pilin Antigenic & Phase Variation

淋病奈瑟氏菌是性传播感染淋病的唯一病原体。一 淋球菌感染的特征之一是缺乏对再次感染的免疫力，即使在反复暴露于 有机体。我们正在研究菌毛蛋白抗原变异的过程，这是一个重要的 淋球菌(GC)发病机制的几个方面。首先，它允许细菌的免疫逃避和持续的 通过感染高危人群/核心人群再次传播。第二，它控制一个人的表达 这种细菌(菌毛)的主要毒力因子。第三，菌毛的功能特性可以 被Pilin Av改变，菌毛在启动定殖化事件中起作用。 我们一直在确定这种人类特有的病原体如何调节高频基因组 重排是Pilin Av的基础。正如我们概述的那样，我们在这个项目上取得了显著的进展 并在理解分子机制方面处于领先地位 任何反病毒系统的背后。在这项资助下，我们在过去发表了13篇同行评议的论文。 3.5年，其中9年与该项目在确定背后机制方面的目标直接相关 皮林大道。在这项优异奖的延展期内，我们会致力于四个主要范畴。首先，我们将 确定我们已经确定的一种新的基因产物在Pilin Av中的功能。第二，我们将定义一个c/S- 我们已将表演场地定义为Pilin Av的必要场所。第三，我们将定义重组 利用我们分离的菌株产生的Pilin Av的中间体，它积累了 干扰生物体的生长。第四，我们将调查为什么苏氨酸中的两个基因失活 Pilin Av的生物合成途径受到干扰。 了解用于指导和控制Pilin Av的机制对于理解这一点是至关重要的 淋病发病机制的一个方面。

Neisseria gonorrhoeas is the only causative agent of the sexually transmitted infection, gonorrhea. One of the hallmarks of gonococcal infection is the lack of immunity to reinfection, even after repeated expose to the organism. We are studying the process of pilin antigenic variation (Av), which is one of the important facets of gonococcal (Gc) pathogenesis. First, it allows immune evasion by the bacterium and continual retransmission through the high risk/core group of infected people. Second, it controls the expression of one of the primary virulence factors of this bacterium (the pilus). Third, the functional properties of the pilus can be altered by pilin Av, and the pilus functions in the initiating events of colonization. We have been determining how this human specific pathogen mediates the high frequency genomic rearrangements that are the basis of pilin Av. We have made outstanding progress on this project as outlined in this document and have developed a leadership position in understanding the molecular mechanisms behind any Av system. We have published 13 peer-reviewed papers with the support of this grant in the past 3.5 years, nine of which are directly related to the goals of this project in determining the mechanisms behind pilin Av. We will pursue four major areas during the extension period of this MERIT Award. First, we will determine how a new gene product we have identified functions in pilin Av. Second, we will define a c/s- acting site we have defined as being essential for pilin Av. Third, we will define the recombination intermediates of pilin Av using strain we have isolated which accumulate intermediate structures that interfere with growth of the organism. Forth, we will investigate why inactivation of two genes in the threonine biosynthesis pathway interfere with pilin Av. Understanding the mechanisms used to direct and control pilin Av is essential to understanding this aspect of the pathogenesis of gonococcal disease.