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四跨膜蛋白在细菌感染中的作用。

The roles of tetraspanins in bacterial infections.

作者信息

Karam Jona, Méresse Stéphane, Kremer Laurent, Daher Wassim

机构信息

Centre National de la Recherche Scientifique UMR 9004, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, Montpellier, France.

Aix Marseille University, CNRS, INSERM, CIML, Marseille, France.

出版信息

Cell Microbiol. 2020 Dec;22(12):e13260. doi: 10.1111/cmi.13260. Epub 2020 Oct 2.

Abstract

Tetraspanins, a wide family composed of 33 transmembrane proteins, are associated with different types of proteins through which they arbitrate important cellular processes such as fusion, adhesion, invasion, tissue differentiation and immunological responses. Tetraspanins share a comparable structural design, which consists of four hydrophobic transmembrane domains with cytoplasmic and extracellular loops. They cooperate with different proteins, including other tetraspanins, receptors or signalling proteins to compose functional complexes at the cell surface, designated tetraspanin-enriched microdomains (TEM). Increasing evidences establish that tetraspanins are exploited by numerous intracellular pathogens as a doorway for entering and replicating within human cells. Although previous surveys focused mainly on viruses and parasites, it is now becoming clear that bacteria interact with tetraspanins, using TEM as a "gateway" to infection. In this review, we examine the biological functions of tetraspanins that are relevant to bacterial infective procedures and consider the available data that reveal how different bacteria benefit from host cell tetraspanins in infection and in the pathogenesis of diseases. We will also emphasise the stimulating potentials of targeting tetraspanins for preventing bacterial infectious diseases, using specific neutralising antibodies or anti-adhesion peptide-based therapies. Such innovative therapeutic opportunities may deliver alternatives for fighting difficult-to-manage and drug-resistant bacterial pathogens.

摘要

四跨膜蛋白是一个由33种跨膜蛋白组成的大家族,它们与不同类型的蛋白质相关联,通过这些蛋白质介导诸如融合、黏附、侵袭、组织分化和免疫反应等重要的细胞过程。四跨膜蛋白具有相似的结构设计,由四个疏水跨膜结构域以及胞质环和胞外环组成。它们与不同的蛋白质协同作用,包括其他四跨膜蛋白、受体或信号蛋白,在细胞表面形成功能性复合物,即富含四跨膜蛋白的微结构域(TEM)。越来越多的证据表明,许多细胞内病原体利用四跨膜蛋白作为进入人体细胞并在其中复制的通道。尽管先前的研究主要集中在病毒和寄生虫上,但现在越来越清楚的是,细菌也与四跨膜蛋白相互作用,将TEM作为感染的“门户”。在这篇综述中,我们研究了与细菌感染过程相关的四跨膜蛋白的生物学功能,并考虑了现有数据,这些数据揭示了不同细菌如何在感染和疾病发病机制中从宿主细胞四跨膜蛋白中获益。我们还将强调使用特异性中和抗体或基于抗黏附肽的疗法靶向四跨膜蛋白以预防细菌感染性疾病的潜在刺激作用。这种创新的治疗机会可能为对抗难以管理的耐药细菌病原体提供替代方案。

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