An unbiased screen to identify Neisseria gonorrhoeae genes important for survival to neutrophil killing mechanisms

鉴定对中性粒细胞杀伤机制生存至关重要的淋病奈瑟菌基因的公正筛选

• 批准号: 10197033
• 负责人: Hank S. SEIFERT
• 金额: $ 27.91万
• 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: 2020-06-17 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10197033
• 关键词: Address; Affect; Apoptosis; Bacteria; Bacterial Proteins; Cells; Collection; Complement; Future; GC gene; Genes; Genetic Screening; Gonorrhea; Growth; Human; Immune system; Infection; Inflammation; Innate Immune Response; Innate Immune System; Leukocytes; Mediating; Methods; Mutation; Neisseria; Neisseria gonorrhoeae; Neisseria meningitidis; Organism; Pathogenesis; Pathogenicity; Pathway interactions; Phenotype; Pilum; Population; Process; Resistance; Signal Transduction; Site; Time; antimicrobial; arm; gene product; mutant; neutrophil; novel; pathogen; pathogenic bacteria; recruit; transmission process

ABSTRACT The human-restricted Neisseria are a collection of related, host-adapted organisms that show a spectrum of pathogenicity, from true commensals to pathogens. The pathogenic species, Neisseria gonorrhoeae and Neisseria meningitidis, have the ability to switch from a more commensal state to produce host damage. Much of the host damage produced by the pathogenic species is the result of host inflammation, particularly, polymorphonuclear leukocytes (PMNs), and these bacteria have evolved many ways to avoid the antimicrobial functions of PMNs. While many studies have identified a number of bacterial genes and gene products that help the Neisseria resist PMN killing processes, many other bacterial species use these gene to resist PMN activities. I propose to conduct an unbiased, genetic screen for novel factors that allow N. gonorrhoeae to resist killing or growth suppression by PMNs to determine mechanisms that have allowed this pathogenic species to resist control by innate immune responses. This screen will provide preliminary results to uncover new mechanisms of N. gonorrhoeae pathogenesis.

摘要 人类限制的奈瑟氏菌是一组相关的、宿主适应的生物的集合， 显示病原性的光谱，从真正的共生体到病原体。致病的 淋球菌和脑膜炎奈瑟氏菌有能力从 更多的共生状态会对寄主造成损害。对宿主造成的大部分损害是由 致病物种是宿主炎症的结果，特别是中性粒细胞。 白细胞(PMN)，这些细菌已经进化出许多方法来避免抗菌剂 PMN的功能。虽然许多研究已经确定了一些细菌基因和基因 帮助奈瑟氏菌抵抗PMN杀死过程的产品，许多其他细菌物种使用 这些基因具有抵抗PMN活性的作用。我建议对小说进行不偏不倚的基因筛选 淋病奈瑟菌抵抗中性粒细胞杀伤或生长抑制的因子 使这种致病物种抵抗先天免疫控制的机制 回应。这一筛选将提供初步结果，以揭示N。 淋病的发病机制。