Targeting the functions of the gonococcal Type lV pilus

项目摘要 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上升，加上最近的急剧增加， 美国报告的病例使这种微生物成为CDC、WHO和NIH的目标。这 建议将重点放在Gc IV型菌毛（T4p）上，这是一种重要的定植， 毒力因子我们将确定T4p如何帮助保护Gc免受多态性 通过改变细菌细胞内的铁稳态来杀死白细胞（PMN）。此外，我们将 进行小分子筛选以鉴定可以抑制蛋白酶所必需的分子， Gc T4p阐述开发新的研究药物，并为 新型化合物的可能性，对GC和可能的其他致病性 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.