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Cross-kingdom activation of Vibrio toxins by ADP-Ribosylation Factor (ARF)-family GTPases.
Journal of Bacteriology ( IF 3.2 ) Pub Date : 2020-11-19 , DOI: 10.1128/jb.00278-20
Alfa Herrera 1 , Karla J F Satchell 2
Affiliation  

Pathogenic Vibrio species use many different approaches to subvert, attack, and undermine the host response. The toxins they produce are often responsible for the devastating effects associated with their diseases. These toxins target a variety of host proteins, which leads to deleterious effects, including dissolution of cell organelle integrity and inhibition of protein secretion. Becoming increasingly prevalent as cofactors for Vibrio toxins are proteins of the small GTPase families. ADP-ribosylation factor small GTPases (ARFs) in particular are emerging as a common host cofactor necessary for full activation of Vibrio toxins. While ARFs are not the direct target of Vibrio cholerae cholera toxin (CT), ARF binding is required for its optimal activity as an ADP-ribosyltransferase. The makes caterpillars floppy (MCF)-like and the domain X (DmX) effectors of the Vibrio vulnificus multifunctional autoprocessing repeats-in-toxin (MARTX) toxin also both require ARFs to initiate autoprocessing and activation as independent effectors. ARFs are ubiquitously expressed in eukaryotes and are key regulators of many cellular processes, and as such they are ideal cofactors for Vibrio pathogens that infect many host species. In this review, we cover in detail the known Vibrio toxins that use ARFs as cross-kingdom activators to both stimulate and optimize their activity. We further discuss how these contrast to toxins and effectors from other bacterial species that coactivate, stimulate, or directly modify host ARFs as their mechanisms of action.

中文翻译:

ADP-核糖基化因子 (ARF) 家族 GTP 酶对弧菌毒素的跨界激活。

致病性弧菌使用许多不同的方法来破坏、攻击和破坏宿主反应。他们产生的毒素通常是造成与其疾病相关的破坏性影响的原因。这些毒素以多种宿主蛋白​​为目标,从而导致有害影响,包括细胞器完整性的溶解和蛋白质分泌的抑制。作为弧菌毒素的辅助因子,越来越普遍的是小 GTP 酶家族的蛋白质。特别是 ADP 核糖基化因子小 GTP 酶 (ARF) 正在成为完全激活弧菌毒素所必需的常见宿主辅助因子。虽然 ARF 不是霍乱弧菌的直接目标霍乱毒素 (CT),ARF 结合是其作为 ADP-核糖基转移酶的最佳活性所必需的。创伤弧菌多功能自动处理重复毒素 (MARTX) 毒素的使毛虫软盘 (MCF) 样和域 X (DmX) 效应器也都需要 ARF 作为独立效应器启动自动处理和激活。ARF 在真核生物中普遍表达,是许多细胞过程的关键调节因子,因此它们是感染许多宿主物种的弧菌病原体的理想辅助因子。在这篇评论中,我们详细介绍了已知的弧菌使用 ARF 作为跨界激活剂来刺激和优化其活动的毒素。我们进一步讨论了这些如何与来自其他细菌物种的毒素和效应物形成对比,这些细菌物种共同激活、刺激或直接修改宿主 ARFs 作为它们的作用机制。
更新日期:2020-11-19
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