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从被忽视到被剖析:技术进步如何引领对柯克斯体病原体发病机制的研究。

From neglected to dissected: How technological advances are leading the way to the study of Coxiella burnetii pathogenesis.

机构信息

IRIM, UMR 9004 CNRS, Université de Montpellier, Montpellier, France.

出版信息

Cell Microbiol. 2020 Apr;22(4):e13180. doi: 10.1111/cmi.13180.

Abstract

Coxiella burnetii is an obligate intracellular bacterial pathogen responsible for severe worldwide outbreaks of the zoonosis Q fever. The remarkable resistance to environmental stress, extremely low infectious dose and ease of dissemination, contributed to the classification of C. burnetii as a class B biothreat. Unique among intracellular pathogens, C. burnetii escapes immune surveillance and replicates within large autophagolysosome-like compartments called Coxiella-containing vacuoles (CCVs). The biogenesis of these compartments depends on the subversion of several host signalling pathways. For years, the obligate intracellular nature of C. burnetii imposed significant experimental obstacles to the study of its pathogenic traits. With the development of an axenic culture medium in 2009, C. burnetii became genetically tractable, thus allowing the implementation of mutagenesis tools and screening approaches to identify its virulence determinants and investigate its complex interaction with host cells. Here, we review the key advances that have contributed to our knowledge of C. burnetii pathogenesis, leading to the rise of this once-neglected pathogen to an exceptional organism to study the intravacuolar lifestyle.

摘要

贝氏考克斯体是一种专性细胞内细菌病原体,可导致动物传染病 Q 热在全球范围内的严重爆发。其对环境压力的极强抗性、极低的感染剂量和易于传播的特性,使其被归类为 B 级生物威胁。与其他细胞内病原体不同的是,贝氏考克斯体能够逃避免疫监视,并在称为包含考克斯体的空泡(Coxiella-containing vacuoles,CCVs)的大型自噬溶酶体样隔室中进行复制。这些隔室的生物发生依赖于对几种宿主信号通路的颠覆。多年来,贝氏考克斯体的专性细胞内特性给其致病特性的研究带来了重大的实验障碍。随着 2009 年无菌培养介质的开发,贝氏考克斯体变得具有遗传可操作性,从而允许实施诱变工具和筛选方法来鉴定其毒力决定因素,并研究其与宿主细胞的复杂相互作用。在这里,我们回顾了促成我们对贝氏考克斯体发病机制的认识的关键进展,这导致了这个曾经被忽视的病原体成为研究细胞内生活方式的特殊生物体。

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