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.

嗜肺军团菌是军团菌病的主要病原体吗？疾病，这是一种严重的、可能致命的肺炎。嗜肺军团菌通过吸入受污染的水滴(例如从空调机组或游泳池)传播。老年人和免疫功能受损的人最容易受到感染，这使军团菌成为医院和公共设施(如疗养院)的主要健康风险。有些令人惊讶的是，尽管嗜肺乳杆菌被确定为社区和医院获得性肺部感染的风险因素，并且英国当局发布了医院水管理指南，但目前英国还没有对其致病机制的研究。军团菌吸入后进入肺细胞，在那里建立一个独特的细胞内生态位，保护细菌免受破坏，使自己得以生存和繁殖。细菌在人类细胞内持续存在的能力是由特殊的细菌蛋白质介导的，这种蛋白质被称为效应器，从细菌细胞注入人类细胞，在那里它们与宿主细胞蛋白质相互作用，并重新编程细胞过程，使细菌受益。了解军团菌效应器颠覆宿主细胞功能的机制对于制定有效的预防和治疗策略至关重要。本项目的目的是研究两个新的军团菌效应子(LtpD和LtpJ)在颠覆宿主细胞功能中的作用，这两个新的军团菌效应子是最近我们对一株重要的临床军团菌进行基因组测序的结果。