Role of Neisseria Gcp in Tfp dynamics and invasion

描述（由申请方提供）：淋病奈瑟菌是一种人类病原体，可在粘膜上长时间持续存在，而不会引起明显的疾病症状。临床和基础研究结果表明，症状感染的发病可能是由于静止和毒力之间的微妙平衡的转变。了N.淋病IV型菌毛（Tfp）在附着的早期阶段起主要作用。TFP启动细菌和宿主之间的多维通讯系统，激活信号通路，降低宿主细胞毒性并增强宿主细胞存活。N.淋病产生糖蛋白酶Gcp，其影响Tfp动力学和侵袭。gcp突变体产生大量捆绑在一起的Tfp纤维，并且这些纤维束以比野生型菌株更高的力收缩。突变体更具侵袭性，这意味着Gcp通常会降低毒力。我们将测试的假设，这些表型是机械相关的，他们有自己的基础，在GCP加工/修改菌毛蛋白（TFP结构亚基）和宿主细胞蛋白。本研究的总体目标是了解影响Tfp介导的感染的细胞生物学和生物物理学的因素，因为它们有可能扰乱宿主和病原体之间的这种平衡。淋病奈瑟菌是一种通过性传播的人类病原体，它可以在粘膜表面长时间存在，而不会引起明显的疾病。一些研究结果表明，症状性淋球菌感染可能是由于在感染早期建立的静止和毒力之间的微妙平衡的转变。本提案的目的是确定奈瑟球菌糖蛋白酶Gcp如何通过其对细菌和宿主细胞蛋白的活性影响这种平衡。

DESCRIPTION (provided by applicant): Neisseria gonorrhoeae is a human pathogen that can persists on the mucosa for lengthy periods without causing overt symptoms of disease. Clinical and basic findings suggest that the onset of sympomatic infection may be due to a shift in the delicate balance between quiescence and virulence. The N. gonorrhoeae Type IV pilus (Tfp) plays a major role in the early stages of attachment. Tfp initiates a multi-dimensional communication system between the bacterium and the host, activating signaling pathways that reduce host cell toxicity and enhance host cell survival. N. gonorrhoeae produces a glycoprotease, Gcp, that affects Tfp dynamics and invasion. The gcp mutant produces Tfp fibers that bundle together in great numbers, and these bundles retract with higher force than the wt strain. The mutant is more invasive, implying that Gcp normally reduces virulence. We will test the hypothesis that these phenotypes are mechanistically related, and that they have their basis in Gcp processing/modification of pilin (the Tfp structural subunit) and host cell proteins. The overall goal of this study is to understand the factors that affect the cell biology and biophysics of Tfp-mediated infection, as they have the potential to disturb this balance between host and pathogen. Project Narrative Neisseria gonorrhoeae, a sexually transmitted pathogen of humans, can persist on the mucosal surface for lengthy periods without causing overt disease. Several findings suggest that symptomatic gonococcal infection may be due to a shift in the delicate balance between quiescence and virulence that had been established early in infection. The aim of this proposal is to determine how the neisserial glycoprotease, Gcp, affects this balance through its activity on bacterial and host cell proteins.