PDF(Pubmed)
Abstract：
Salmonella enterica is a leading cause of bacterial food-borne illness in humans and is responsible for millions of cases annually. A critical strategy for the survival of this pathogen is the translocation of bacterial virulence factors termed effectors into host cells, which primarily function via protein-protein interactions with host proteins. The Salmonella genome encodes several paralogous effectors believed to have arisen from duplication events throughout the course of evolution. These paralogs can share structural similarities and enzymatic activities but have also demonstrated divergence in host cell targets or interaction partners and contributions to the intracellular lifecycle of Salmonella. The paralog effectors SopD and SopD2 share 63% amino acid sequence similarity and extensive structural homology yet have demonstrated divergence in secretion kinetics, intracellular localization, host targets, and roles in infection. SopD and SopD2 target host Rab GTPases, which represent critical regulators of intracellular trafficking that mediate diverse cellular functions. While SopD and SopD2 both manipulate Rab function, these paralogs display differences in Rab specificity, and the effectors have also evolved multiple mechanisms of action for GTPase manipulation. Here, we highlight this intriguing pair of paralog effectors in the context of host-pathogen interactions and discuss how this research has presented valuable insights into effector evolution.
摘要：
肠沙门氏菌是人类细菌性食源性疾病的主要原因，每年造成数百万例病例。该病原体生存的关键策略是将称为效应子的细菌毒力因子转移到宿主细胞中。主要通过与宿主蛋白的蛋白-蛋白相互作用起作用。沙门氏菌基因组编码几种旁系效应子，据信这些效应子是在整个进化过程中由复制事件引起的。这些旁系同源物可以共享结构相似性和酶活性，但也显示出宿主细胞靶标或相互作用伙伴的差异以及对沙门氏菌细胞内生命周期的贡献。同源效应子SopD和SopD2共有63%的氨基酸序列相似性和广泛的结构同源性，但在分泌动力学方面表现出差异。细胞内定位，主机目标,以及在感染中的作用。SopD和SopD2目标宿主RabGTPases，它们代表了介导多种细胞功能的细胞内运输的关键调节剂。虽然SopD和SopD2都操纵Rab函数，这些旁系同源物显示出Rab特异性的差异，效应子也进化出了多种操作GTP酶的作用机制。这里,我们在宿主-病原体相互作用的背景下重点介绍了这对有趣的旁系效应子，并讨论了这项研究如何为效应子进化提供有价值的见解。
