Neisseria gonorrhoeae G4-binding proteins that regulate pilin antigenic variation

描述（由申请人提供）：淋病奈瑟菌毛的抗原变异是难以获得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样重组途径，也依赖于pilE启动子上游G4结构的形成，但确切的机制尚不清楚。G4结构在细胞中的作用仍然存在争议，了解pilE G4如何影响抗原性变异将有助于G4结构被认为具有生物学相关性。该项目的目标是鉴定和表征在体内协助形成、稳定性和分辨率的pilE G4 DNA结构的蛋白质。其中一种新蛋白可能成为预防淋球菌感染复发的潜在药物靶点。

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.