Targeting the functions of the gonococcal Type lV pilus

项目总结 淋病奈瑟菌(GC)是性传播感染的唯一病原体。 淋病。抗生素耐药性的迅速增加加上最近的急剧增加 美国报告的病例使这种细菌成为疾控中心、世卫组织和美国国立卫生研究院的目标。这 提案将侧重于GCIV型菌毛(T4p)，这是一种基本的殖民和 毒力因子。我们将确定T4p如何帮助保护GC免受中性粒细胞的伤害 白血球(PMN)通过改变细菌细胞内的铁稳态来杀死。此外，我们还将 进行小分子筛选以确定可以抑制一种必需的蛋白酶的分子 GC T4p精细化开发新型药理制剂用于研究，并为 可能有新类型的化合物对GC和可能的其他致病物质起作用 细菌。

PROJECT SUMMARY Neisseria gonorrhoeae (Gc) is the sole causative agent of the sexually transmitted infection gonorrhea. The rapid raise in antibiotic resistance coupled with a recent sharp increase in reported cases in the U.S. have made this organism a target for the CDC, WHO and NIH. This proposal will focus on the Gc Type IV pilus (T4p), which is an essential colonization and virulence factor. We will determine how the T4p helps to protect Gc from polymorphonuclear leucocyte (PMN) killing by altering iron homeostasis within the bacterial cell. Additionally, we will perform a small molecule screen to identify molecules that can inhibit a protease necessary for Gc T4p elaboration to develop novel pharmacologic agent for research and set the stage for the possibility for new types of compounds that act against Gc and possibly other pathogenic bacteria.