The roles of the Legionella pneumophila effectors PieE and LtpG in formation and maintenance of the Legionella containing vacuole

嗜肺军团菌效应器 PieE 和 LtpG 在含军团菌空泡形成和维持中的作用

• 批准号: MR/L018225/1
• 负责人: Gad Frankel
• 金额: $ 61.18万
• 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: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FL018225%2F1
• 关键词: roles; Legionella; pneumophila; effectors; PieE

Legionella pneumophila is the major causative agent of Legionnaires' disease, which is a severe, potentially fatal, form of pneumonia. The 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). The potentially fast and wide dissemination of Legionella by airflow can lead to large outbreaks, as was seen in Edinburgh and Stoke-on-Trent in 2012, affecting dozens to hundreds of persons. Infectious sources of these outbreaks are often hard to trace and therefore difficult to eradicate, making Legionella an important health risk for densely-populated areas.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 bacteria 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. By focusing our investigation on two important effectors, PieE and LtpG, we aim to reveal fundamental mechanisms employed by the bacteria to thrive in their host cells and cause disease.

嗜肺军团菌是军团病的主要病原体，军团病是一种严重的、可能致命的肺炎形式。细菌通过吸入受污染的水滴（例如来自空调机组或游泳池）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（如疗养院）的主要健康风险。军团菌可能通过气流快速和广泛传播，可能导致大规模爆发，如2012年在爱丁堡和特伦特河畔斯托克发生的情况，影响数十至数百人。这些疾病爆发的传染源通常难以追踪，因此难以根除，使军团菌成为人口密集地区的一个重要健康风险。军团菌吸入人体后进入肺细胞，在那里建立一个独特的细胞内生态位，保护细菌免受破坏，使其自身存活和繁殖。细菌在人类细胞内持续存在的能力是由称为效应子的特殊细菌蛋白质介导的，这些蛋白质从细菌细胞注射到人类细胞中，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以使细菌受益。了解军团菌效应子破坏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。通过将我们的研究集中在两个重要的效应子PieE和LtpG上，我们的目标是揭示细菌在其宿主细胞中茁壮成长并引起疾病的基本机制。

项目成果

Creating a customized intracellular niche: subversion of host cell signaling by Legionella type IV secretion system effectors.

创建定制的细胞内生态位：军团菌 IV 型分泌系统效应器颠覆宿主细胞信号传导。

• DOI: 10.1139/cjm-2015-0166
• 发表时间: 2015
• 期刊: Canadian journal of microbiology
• 影响因子: 2.8
• 作者: So EC

The Legionella effector LtpM is a new type of phosphoinositide-activated glucosyltransferase

• DOI: 10.1074/jbc.ra118.005952
• 发表时间: 2019-02-22
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Levanova, Nadezhda;Mattheis, Corinna;Schroeder, Gunnar Neels
• 通讯作者: Schroeder, Gunnar Neels

Determination of In Vivo Interactomes of Dot/Icm Type IV Secretion System Effectors by Tandem Affinity Purification.

通过串联亲和纯化测定 Dot/Icm IV 型分泌系统效应子的体内相互作用。

• DOI: 10.1007/978-1-4939-9048-1_19
• 发表时间: 2019
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: So EC

The Rab-binding Profiles of Bacterial Virulence Factors during Infection.

• DOI: 10.1074/jbc.m115.700930
• 发表时间: 2016-03-11
• 期刊: The Journal of biological chemistry
• 作者: So EC;Schroeder GN;Carson D;Mattheis C;Mousnier A;Broncel M;Tate EW;Frankel G
• 通讯作者: Frankel G