Mechanisms of Gonococcal Pilin Antigenic & Phase Variation

淋病奈瑟菌是性传播感染淋病的唯一病原体。一 淋球菌感染的标志之一是即使在反复接触淋球菌后，也缺乏对再次感染的免疫力。 有机体我们正在研究菌毛蛋白抗原变异（Av）的过程，这是菌毛蛋白抗原变异的重要机制之一。 淋球菌（Gc）发病机制的方面。首先，它允许细菌的免疫逃避， 通过高危/核心感染人群传播。第二，它控制着一个人的表达， 这种细菌的主要毒力因子（菌毛）。第三，菌毛的功能特性可以 被pilin Av改变，并且菌毛在定殖的起始事件中起作用。 我们一直在确定这种人类特异性病原体是如何介导高频率基因组 重排的基础上pilin Av.我们在这个项目上取得了突出的进展， 并在理解分子机制方面处于领导地位 在任何AV系统之后。我们在过去的资助下发表了13篇同行评议的论文 3.5其中9年与本项目的目标直接相关， 皮林大道在此优异奖的延长期内，我们将在四个主要领域开展工作。一是 确定我们已经鉴定的新基因产物在菌毛蛋白Av中的功能。其次，我们将定义一个c/s- 作用位点，我们已经定义为必不可少的菌毛Av。第三，我们将定义重组 使用我们已经分离的菌株的菌毛蛋白Av的中间体，其积累了中间体结构， 干扰有机体的生长。第四，我们将研究为什么苏氨酸中的两个基因失活， 生物合成途径干扰菌毛蛋白Av. 了解用于指导和控制菌毛蛋白Av的机制对于理解这一点至关重要 淋球菌病的发病机制方面。

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.