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.

抽象的 人类限制的奈瑟菌是一组相关的、适应宿主的生物体， 显示出一系列致病性，从真正的共生体到病原体。致病性 淋病奈瑟菌和脑膜炎奈瑟菌有能力从 更多的共生状态产生宿主损害。大部分宿主损害是由 致病物种是宿主炎症的结果，特别是多形核 白细胞（PMN），这些细菌已经进化出许多方法来避免抗菌药物 PMN 的功能。虽然许多研究已经鉴定出许多细菌基因和基因 帮助奈瑟菌抵抗 PMN 杀灭过程的产品，许多其他细菌物种都使用 这些基因可以抵抗PMN活动。我建议对新颖的基因进行公正的基因筛选 允许淋病奈瑟菌抵抗 PMN 杀伤或生长抑制的因素，以确定 允许这种致病物种抵抗先天免疫控制的机制 回应。该筛选将提供初步结果以揭示 N. 淋病发病机制。