Reconceptualizing the chlamydial inclusion as a pathogen-specified parasitic organelle: an expanded role for Inc proteins.

Reconceptualizing the chlamydial inclusion as a pathogen-specified parasitic organelle: an expanded role for Inc proteins.
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DOI:
10.3389/fcimb.2014.00157
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发表时间:
2014
影响因子:
5.7
通讯作者:
Ouellette SP
Ouellette SP
中科院分区:
医学2区
文献类型:
--
作者:
Moore ER;Ouellette SP

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衣原体是一种专有的细胞内病原体,在宿主细胞内形成一个空泡,称为衣原体包涵体。衣原体包涵体的流行概念是寄生性液泡。在这里,包涵体是单向宿主-病原体相互作用的接受者,从而从细胞中吸取营养物质并对其产生负面影响。虽然衣原体协调细胞功能的某些方面,但最近的数据表明,宿主细胞在衣原体排出之前甚至之后都保持健康。因此,虽然衣原体依赖宿主细胞提供必要的代谢物,但宿主细胞在衣原体生长和发育过程中的整体功能并未受到严重干扰。这与专性细胞内有机体维持其宿主的生存能力的利益是一致的。为此,衣原体表达包涵膜蛋白Incs,作为包涵膜的分子标志物。INCS还有助于包涵体膜的物理结构,并促进跨越包涵体膜的宿主与病原体的相互作用。考虑到Incs的功能和在包涵体膜上发生的动态相互作用,我们认为包涵体的行为类似于细胞器-尽管对病原体有利。我们提出的假设是,衣原体包涵体作为病原体特异性的寄生细胞器。这种表达方式将包涵体整合到现有的亚细胞转运途径中,以转移宿主衍生的代谢物的子集,从而维持宿主细胞的动态平衡。我们回顾了衣原体包涵体与宿主细胞的已知相互作用,并讨论了Inc蛋白在这一模型中的作用,以及这一观点如何影响对这些蛋白的研究。从衣原体特有的寄生细胞器中学到的经验可以应用于其他细胞内的病原体。这将增加我们对细胞内病原体如何与宿主细胞建立其独特的发育生态位的理解。
Chlamydia is an obligate intracellular pathogen that develops in the host cell in a vacuole termed the chlamydial inclusion. The prevailing concept of the chlamydial inclusion is of a parasitophorous vacuole. Here, the inclusion is the recipient of one-way host-pathogen interactions thus draining nutrients from the cell and negatively impacting it. While Chlamydia orchestrates some aspects of cell function, recent data indicate host cells remain healthy up until, and even after, chlamydial egress. Thus, while Chlamydia relies on the host cell for necessary metabolites, the overall function of the host cell, during chlamydial growth and development, is not grossly disturbed. This is consistent with the obligate intracellular organism's interest to maintain viability of its host. To this end, Chlamydia expresses inclusion membrane proteins, Incs, which serve as molecular markers for the inclusion membrane. Incs also contribute to the physical structure of the inclusion membrane and facilitate host-pathogen interactions across it. Given the function of Incs and the dynamic interactions that occur at the inclusion membrane, we propose that the inclusion behaves similarly to an organelle-albeit one that benefits the pathogen. We present the hypothesis that the chlamydial inclusion acts as a pathogen-specified parasitic organelle. This representation integrates the inclusion within existing subcellular trafficking pathways to divert a subset of host-derived metabolites thus maintaining host cell homeostasis. We review the known interactions of the chlamydial inclusion with the host cell and discuss the role of Inc proteins in the context of this model and how this perspective can impact the study of these proteins. Lessons learnt from the chlamydial pathogen-specified parasitic organelle can be applied to other intracellular pathogens. This will increase our understanding of how intracellular pathogens engage the host cell to establish their unique developmental niches.
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