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: 10058123
• 负责人: Hank S. SEIFERT
• 金额: $ 15.8万
• 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 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10058123
• 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 人类限制性奈瑟菌是一组相关的适应宿主的生物体， 显示出一系列的致病性，从真正的病原体到病原体。致病 淋病奈瑟菌和脑膜炎奈瑟菌具有从 更易产生宿主损伤。大部分由病毒引起的宿主损害 病原性物种是宿主炎症的结果，特别是多形性 白细胞（PMNs），这些细菌已经进化出许多方式来避免抗生素 PMNs的功能。虽然许多研究已经确定了一些细菌基因和基因 产品，帮助奈瑟菌抵抗中性粒细胞杀伤过程，许多其他细菌物种使用 这些基因抵抗PMN活动。我建议进行一次无偏见的基因筛查， 这些因素使N。淋病抵抗杀伤或生长抑制的中性粒细胞，以确定 这些机制使这种致病物种能够抵抗先天免疫系统的控制， 应答本研究为揭示N. 淋病发病机制