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开始理解 IV 型分泌系统效应蛋白在柯克斯体感染发病机制中的作用。

Beginning to Understand the Role of the Type IV Secretion System Effector Proteins in Coxiella burnetii Pathogenesis.

机构信息

Mikrobiologisches Institut-Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Wasserturmstraße 3/5, 91054, Erlangen, Germany.

Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

出版信息

Curr Top Microbiol Immunol. 2017;413:243-268. doi: 10.1007/978-3-319-75241-9_10.

DOI:10.1007/978-3-319-75241-9_10
PMID:29536362
Abstract

Coxiella burnetii is the etiological agent of the zoonotic disease Q fever, which manifests in severe outbreaks and is associated with important health and economic burden. Moreover, C. burnetii belongs to the list of class B bioterrorism organisms, as it is an airborne and highly infective pathogen with remarkable resistance to environmental stresses. Detailed study of the host-pathogen interaction during C. burnetii infection has been hampered due to the obligate intracellular nature of this pathogen. However, the development of an axenic culture medium, together with the implementation of bioinformatics tools and high-content screening approaches, have significantly progressed C. burnetii research in the last decade. This has facilitated identification of the Dot/Icm type IV secretion system (T4SS) as an essential virulence factor. T4SS is used to deliver an arsenal of effector proteins into the cytoplasm of the host cell. These effectors mediate the survival of the host cell and the development of very large replicative compartments called Coxiella-containing vacuoles (CCVs). Biogenesis of the CCV relies on T4SS-dependent re-routing of numerous intracellular trafficking pathways to deliver membranes and nutrients that are essential for bacterial replication. This review aims to illustrate the key milestones that have contributed to ascribe C. burnetii as a model organism for the study of host/pathogen interactions as well as presenting an up-to-date description of our knowledge of the cell biology of C. burnetii infections.

摘要

贝氏考克斯体是引起人畜共患病 Q 热的病原体,该病具有严重的暴发特征,并给人类健康和经济带来重大负担。此外,贝氏考克斯体被列入 B 类生物恐怖主义生物制剂名单,因为它是一种空气传播的、高度感染性的病原体,具有很强的环境压力抗性。由于这种病原体必须在细胞内生存,因此对其感染过程中的宿主-病原体相互作用的详细研究受到了阻碍。然而,在过去十年中,由于无细胞培养基的开发,以及生物信息学工具和高通量筛选方法的应用,贝氏考克斯体的研究取得了显著进展。这有助于确定 Dot/Icm 型 IV 型分泌系统(T4SS)是一种必需的毒力因子。T4SS 用于将一系列效应蛋白输送到宿主细胞质中。这些效应蛋白介导宿主细胞的存活和非常大的复制性隔室(称为包含考克斯体的空泡(CCV))的发育。CCV 的生物发生依赖于 T4SS 依赖性重新路由许多细胞内运输途径,以输送对细菌复制至关重要的膜和营养物质。这篇综述旨在说明促成将贝氏考克斯体作为研究宿主/病原体相互作用的模式生物的关键里程碑,并介绍对贝氏考克斯体感染的细胞生物学的最新描述。

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