The Legionella pneumophila type IV secretion system effector proteins LtpD and LtpJ

嗜肺军团菌 IV 型分泌系统效应蛋白 LtpD 和 LtpJ

• 批准号: G1001729/1
• 负责人: Gad Frankel
• 金额: $ 48.55万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1001729%2F1
• 关键词: Legionella; pneumophila; type; IV; secretion

Legionella pneumophila is the major causative agent of Legionnaires? disease, which is a severe, potentially fatal, form of pneumonia. Legionella pneumophila bacteria are transmitted via inhalation of contaminated water droplets (e.g. from air-conditioning units or swimming pools). The elderly and immunocompromised are most susceptible to infection, making Legionella a major health risk in hospitals and communal facilities (e.g. nursing homes). Somewhat surprisingly, despite the identification of L. pneumophila as a risk factor for community and nosocomial acquired pulmonary infections, and the guidelines for water management in hospitals issued by the UK authorities, no research into the mechanisms by which it causes disease is currently underway in the UK. Following its inhalation, Legionella enters lung cells where it establishes a unique intracellular niche that protects the bacterium from destruction, allowing its own survival and multiplication. The ability of the bacterium to persist within human cells is mediated by special bacterial proteins, known as effectors, which are injected from the bacterial cell into the human cell where they interact with host cell proteins and re-programme cellular processes for the benefit of the bacterium. Understanding the mechanism by which Legionella effectors subvert host cell functions is essential for development of effective prevention and treatment strategies. The aim of this project is to study the role two novel Legionella effectors (LtpD and LtpJ), recently identified as a result of our genome sequencing of an important clinical Legionella isolate, play in subversion of the host cells functions.

肺孢子虫是军团征收的主要病因吗？疾病是一种严重的，可能致命的肺炎形式。肺炎军团细菌是通过吸入受污染的水滴（例如，来自空调单元或游泳池）传播。老年人和免疫功能低下的人最容易感染，使军团菌成为医院和公共设施的主要健康风险（例如疗养院）。令人惊讶的是，尽管将肺炎李斯特拉乳杆菌鉴定为社区和性交获得的肺部感染的危险因素，以及英国当局发行的医院水管理指南，但没有研究英国目前正在进行IT原因疾病的机制。吸入后，军团菌进入肺部细胞，在那里建立了独特的细胞内细胞生态位，可保护细菌免受破坏，允许其自身的生存和繁殖。细菌在人类细胞中持续存在的能力是由特殊的细菌蛋白（称为效应子）介导的，这些蛋白被称为效应子，这些蛋白质从细菌细胞中注射到人类细胞中，在那里它们与宿主细胞蛋白相互作用并重新制作细胞过程，以使细菌受益。了解军团菌效应子颠覆宿主细胞功能的机制对于开发有效的预防和治疗策略至关重要。该项目的目的是研究两个新型军团菌效应子（LTPD和LTPJ），该作用最近是由于我们对重要的临床军团菌分离株的基因组测序而被鉴定出来的，在抑制宿主细胞功能中起作用。