Spanò Stefania, Galán Jorge E
a Institute of Medical Sciences, University of Aberdeen , Foresterhill , Aberdeen , UK.
b Department of Microbial Pathogenesis , Yale University School of Medicine , New Haven , CT , USA.
Small GTPases. 2018 Mar 4;9(1-2):182-191. doi: 10.1080/21541248.2017.1336192. Epub 2017 Jul 5.
Intracellular bacterial pathogens survive and replicate within specialized eukaryotic cell organelles. To establish their intracellular niches these pathogens have adopted sophisticated strategies to control intracellular membrane trafficking. Since Rab-family GTPases are critical regulators of endocytic and secretory membrane trafficking events, many intracellular pathogens have evolved specific mechanisms to modulate or hijack Rab GTPases dynamics and trafficking functions. One such strategy is the delivery of bacterial effectors through specialized machines to specifically target Rab GTPases. Some of these effectors functionally mimic host proteins that regulate the Rab GTP cycle, while others regulate Rabs proteins through their post-translation modifications or proteolysis. In this review, we examine how the localization and function of Rab-family GTPases are altered during infection with 3 well-studied intracellular bacterial pathogens, Mycobacterium tuberculosis, Salmonella enterica and Legionella pneumophila. We also discuss recent findings about specific mechanisms by which these intracellular pathogens target this protein family.
细胞内细菌性病原体在特定的真核细胞器内存活并复制。为了建立其细胞内生态位,这些病原体采用了复杂的策略来控制细胞内膜运输。由于Rab家族GTP酶是内吞和分泌膜运输事件的关键调节因子,许多细胞内病原体已经进化出特定机制来调节或劫持Rab GTP酶的动力学和运输功能。一种这样的策略是通过专门的机器传递细菌效应蛋白,以特异性靶向Rab GTP酶。其中一些效应蛋白在功能上模拟调节Rab GTP循环的宿主蛋白,而其他效应蛋白则通过其翻译后修饰或蛋白水解来调节Rab蛋白。在这篇综述中,我们研究了在感染三种经过充分研究的细胞内细菌性病原体(结核分枝杆菌、肠炎沙门氏菌和嗜肺军团菌)期间,Rab家族GTP酶的定位和功能是如何改变的。我们还讨论了关于这些细胞内病原体靶向这个蛋白家族的具体机制的最新发现。