Neisseria gonorrhoeae G4-binding proteins that regulate pilin antigenic variation

描述(申请人提供)：淋球菌菌毛的抗原性变异是很难实现长期免疫的原因之一，因为宿主可能会再次感染。Av既依赖于RECF样的重组途径，也依赖于桩基启动子上游G4结构的形成，但确切的机制仍不清楚。G4结构在细胞中的作用仍然存在争议，了解G4堆如何影响抗原变异将有助于G4结构被认为是生物学相关的。该项目的目标是鉴定和表征在体内帮助形成、稳定和分辨堆G4DNA结构的蛋白质。这些新蛋白中的一种可能成为预防淋球菌复发感染的潜在药物靶点。 公共卫生相关性：通过改变其表面菌毛，致病细菌淋球菌可以感染以前治愈的宿主。菌毛蛋白的抗原变异是一种基因转换事件，它依赖于重组蛋白和表达菌毛基因上游的16个碱基的鸟嘌呤四元组(G4)结构。这项工作旨在确定参与菌毛蛋白抗原变异的两个解旋酶是否与G4结构特异地相互作用，并识别在启动抗原变异中发挥作用的新的G4结合蛋白。

DESCRIPTION (provided by applicant): Antigenic variation of the N. gonorrhoeae pilus is one of the reasons why long term immunity is difficult to achieve, as hosts can get reinfected. Av is dependent on both the RecF-like recombination pathway and the formation of a G4 structure upstream of the pilE promoter, but the exact mechanism is still unknown. The role of G4 structures in the cell is still controversial and understanding how the pilE G4 affects antigenic variation would help G4 structures to be accepted as biologically relevant. The goal of this project is to identify and characterize the proteins that assist in formation, stability, and resolution of the pilE G4 DNA structure in vivo. One of these new proteins could be a potential drug target for preventing recurring gonococcal infections. PUBLIC HEALTH RELEVANCE: By changing their surface pili, the pathogenic bacterium Neisseria gonorrhoeae can infect previously cured hosts. Pilin antigenic variation is a gene conversion event that is dependent on recombination proteins as well as a 16 bp guanine quartet (G4) structure upstream of the expressed pilus gene. The work proposed in this fellowship seeks to establish whether two helicases involved in pilin antigenic variation interact specifically with the G4 structure, and to identify novel G4-binding proteins that play a role in initiating antigenic variation.