The Cytolethal Distending Toxin Contributes to Microbial Virulence and Disease Pathogenesis by Acting As a Tri-Perditious Toxin.
The Cytolethal Distending Toxin Contributes to Microbial Virulence and Disease Pathogenesis by Acting As a Tri-Perditious Toxin.
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DOI：
10.3389/fcimb.2016.00168
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发表时间：
2016
影响因子：
5.7
通讯作者：
Shenker BJ
中科院分区：
文献类型：
--
作者：
Scuron MD;Boesze-Battaglia K;Dlakić M;Shenker BJ
本文综述了细胞致死性膨胀毒素（Cdt）作为毒力因子在产毒病原体致病中的作用的研究现状和进展。一个主要的重点是这次审查的结构和功能之间的关系，包括AB 2 Cdt全毒素的各个亚基。特别是，我们专注于这种毒素的分子机制的特点，并占Cdt中毒多种细胞类型的能力，利用细胞膜上无处不在的结合伙伴。此外，我们提出了一个范式转变的分子模式的行动，其中的活性Cdt亚基，CdtB，能够阻止一个关键的信号级联，从而导致的结果的基础上编程和磷脂酰肌醇3-激酶（PI-3 K）在各种细胞中的作用。基于集体Cdt文献，我们现在提出Cdt是一种独特且有效的毒力因子，能够作为三重毒素，通过以下方式损害宿主防御：（1）破坏上皮屏障;（2）抑制获得性免疫;（3）促进促炎反应。因此，Cdt通过促进持久性和损害宿主消除，在促进感染的早期阶段和疾病进展的后期阶段中发挥关键作用。
This review summarizes the current status and recent advances in our understanding of the role that the cytolethal distending toxin (Cdt) plays as a virulence factor in promoting disease by toxin-producing pathogens. A major focus of this review is on the relationship between structure and function of the individual subunits that comprise the AB2 Cdt holotoxin. In particular, we concentrate on the molecular mechanisms that characterize this toxin and which account for the ability of Cdt to intoxicate multiple cell types by utilizing a ubiquitous binding partner on the cell membrane. Furthermore, we propose a paradigm shift for the molecular mode of action by which the active Cdt subunit, CdtB, is able to block a key signaling cascade and thereby lead to outcomes based upon programming and the role of the phosphatidylinositol 3-kinase (PI-3K) in a variety of cells. Based upon the collective Cdt literature, we now propose that Cdt is a unique and potent virulence factor capable of acting as a tri-perditious toxin that impairs host defenses by: (1) disrupting epithelial barriers; (2) suppressing acquired immunity; (3) promoting pro-inflammatory responses. Thus, Cdt plays a key role in facilitating the early stages of infection and the later stages of disease progression by contributing to persistence and impairing host elimination.