MECHANISMS OF GONOCOCCAL PILIN ANTIGENIC/PHASE VARIATION

性状（改编自申请人摘要）：淋病奈瑟菌 (Gc)是一种专性的人类病原体，是病原体的病原体， 性传播疾病淋病 所有新鲜分离的Gc表达 细胞表面的皮利;而菌毛的表达是 感染人类志愿者。 GC皮利最独特的特征是 单个生物体可能具有大量的菌毛抗原类型， 可以生产。 这种抗原变异过程是通过重组发生的 几个沉默的菌毛蛋白基因拷贝之一和单一表达的 基因（编码菌毛的主要亚基，菌毛蛋白），导致 表达的基因和蛋白质中的多个序列变化。 的这个系统 菌毛蛋白抗原变异在Gc中提供了大量的抗原类型嵌合体， 人口，并允许持续再感染的高风险部分， 将Gc传播到一般人群中的人群。 我们对产生和控制 菌毛蛋白的抗原变异是通过确定 当抗原转换发生时，序列发生变化。 为每个 抗原开关，19个沉默菌毛蛋白基因拷贝之一的一部分， 以非相互的方式转移到pilE基因座。 调查人员 已经分离出许多顺式和反式作用突变， 菌毛蛋白抗原变异的过程，并预测 促进可变菌毛蛋白序列的高频转移。 他们将 继续分离和鉴定基因、蛋白质和顺式作用DNA 菌毛蛋白抗原变异所需的序列，以测试 关于菌毛蛋白抗原变异是如何介导的不同假说。 他们 还将探讨菌毛蛋白抗原变异是 在人类感染过程中受到调节。 通过这些调查， 该项目将继续定义用于允许这些的分子机制 高频复合反应对于 淋病的发病机理

DESCRIPTION (Adapted from the applicant's abstract): Neisseria gonorrhoeae (Gc) is an obligate human pathogen that is the causative agent of the sexually transmitted disease gonorrhea. All freshly isolated Gc express pili on their cell surfaces; and the expression of the pilus is required for infection in human volunteers. The most unique characteristic of Gc pili is the large number of possible pilus antigenic types that a single organism can produce. This antigenic variation process occurs by recombination between one of several silent pilin gene copies and the singular expressed gene (that encodes the major subunit of the pilus, pilin), resulting in multiple sequence changes in the expressed gene and protein. This system of pilin antigenic variation provides a large mosaic of antigenic types in a Gc population, and allows continual reinfection of the high risk portion of the human population that transmits Gc into the general population. Much of our understanding about the mechanisms that produce and control pilin antigenic variation has been obtained by determining the types of sequence changes that occur when an antigenic switch occurs. For each antigenic switch, a portion of one of 19 silent pilin gene copies is transferred to the pilE locus in a nonreciprocal fashion. The investigators have isolated a number of cis and trans-acting mutation that disrupt the process of pilin antigenic variation and predict molecular mechanisms that promote the high frequency transfer of variable pilin sequences. They will continue to isolate and characterize genes, proteins, and cis-acting DNA sequences that are required for pilin antigenic variation to test between different hypotheses about how pilin antigenic variation is mediated. They will also explore the possibility that pilin antigenic variation is regulated during human infection. Through these investigations, this project will continue to define the molecular mechanism used to allow these high frequency recombination reactions that are of critical importance to the pathogenesis of gonorrhea.