Targeting the functions of the gonococcal Type lV pilus

针对 IV 型淋球菌菌毛的功能

• 批准号: 10663812
• 负责人: Hank S. SEIFERT
• 金额: $ 56.29万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10663812
• 关键词: Address; Antibiotic Resistance; Antibiotics; Bacteria; Binding; Case Study; Cells; Chemicals; Coupled; Cytoplasm; DNA; Data; Disease; Drug Kinetics; Enzymes; Epithelium; Evaluation; Fiber; Future; Genes; Genetic Transformation; Gonorrhea; Homeostasis; Human; Infection; Iron; Knowledge; Leukocytes; Locomotion; Mediating; Metalloproteases; Microbial Biofilms; Molecular; Mus; Neisseria gonorrhoeae; Organism; Pathogenesis; Peptide Hydrolases; Phenotype; Pilum; Property; Public Health; Reporting; Research; Resistance; Sexually Transmitted Agents; Sexually Transmitted Diseases; Site; Specificity; System; Testing; Tissues; Toxic effect; Traction; Type IV Secretion System Pathway; Uncertainty; United States National Institutes of Health; Virulence; Virulence Factors; Virulent; Work; Zinc; antimicrobial; cell motility; innovation; mutant; neutrophil; novel; pathogen; pathogenic bacteria; pharmacologic; physical property; recruit; small molecule; small molecule inhibitor; translational approach

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.

项目概要 淋病奈瑟菌 (Gc) 是性传播感染的唯一病原体 淋病。抗生素耐药性迅速增加，加上最近抗生素耐药性急剧增加 美国报告的病例已使这种生物体成为 CDC、WHO 和 NIH 的目标。这 提案将重点关注 Gc IV 型菌毛 (T4p)，这是一种重要的定殖和 毒力因子。我们将确定 T4p 如何帮助保护 Gc 免受多形核的影响 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，以确定可以抑制蛋白酶所需的分子 Gc T4p 的详细阐述，旨在开发用于研究的新型药物制剂，并为 对抗 Gc 和其他病原体的新型化合物的可能性 细菌。