MOLECULAR ANALYSIS OF GONOCOCCAL RECA FUNCTIONS

描述：(改编自申请者的摘要)奈瑟里亚 淋病(Gc)是一种人类特有的病原体。 性传播疾病淋病的代理人。这是革兰氏阴性 双球菌自然只在人类体内发现，它有几个 有趣的生物学特性。GC的系统发育分析表明 它与大多数其他研究得很好的革兰氏阴性细菌相去甚远。 所有新鲜的人类GC分离株都在其细胞表面表达菌毛，并且 菌毛的表达是人类感染所必需的 志愿者。GC菌毛的一个不同寻常的特征是数量多 单个生物体可能产生的菌毛抗原类型 (抗原性变异)。 这一抗原变异过程是通过DNA重组发生的 几个沉默的菌毛蛋白基因拷贝和单个表达的基因 (它编码了菌毛的主要亚基，Pilin)，结果是 表达的基因和蛋白发生多重序列变化。打桩 抗原变异在GC中提供了大量的抗原类型马赛克 人群，并允许高危部分持续再次感染 将GC传播到普通人群的人类人口的比例。 这个抗原变异系统需要GC的RecA蛋白，也是如此 DNA转化和DNA修复，但很大程度上还不清楚RecA是如何 在这些过程中发挥作用。当GC recA突变体与 E.Coli(EC)recA基因，依赖RecA的三个GC过程是 不同的补充：EC RecA不能补充DNA修复， 但DNA转化的补体和毛细蛋白的超补体 变种。这项提议将定义这些物质的分子基础 发散互补表型，决定是否存在 GC和EC RecA之间的生化差异，并确定是否存在 是蛋白质-蛋白质相互作用的差异解释了 交替的互补模式。这些研究将有助于 了解淋球菌的发病机制，并帮助定义GC和 EC RecA蛋白介导不同的细胞过程。

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. This gram-negative diplococcus is naturally found only within humans and has several interesting biological properties. Phylogenetic analysis of Gc indicate that it is distant from most other well studied gram-negative bacteria. All fresh human isolates of Gc express pili on their cell surfaces, and the expression of the pilus is required for infection in human volunteers. One unusual characteristic of Gc pili is the large number of possible pilus antigenic types that a single organism can produce (antigenic variation). This antigenic variation process occurs by DNA 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. 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. This antigenic variation system requires the RecA protein of Gc, as does DNA transformation and DNA repair, but it is largely unknown how RecA acts in these processes. When a Gc recA mutant is complemented with the E. coli (Ec) recA gene, the three RecA-dependent Gc processes are complemented differently: Ec RecA does not complement for DNA repair, but complements for DNA transformation, and hyper-complements for pilin variation. This proposal will define the molecular basis for these divergent complementation phenotypes, determine whether there are biochemical differences between Gc and Ec RecA, and determine if there are differences in protein-protein interactions that explain the alternate complementation patterns. These studies will aid in the understanding of gonococcal pathogenesis, and help define how the Gc and Ec RecA proteins mediate different cellular processes.