The Salmonella Effector SseK3 Targets Small Rab GTPases
The Salmonella Effector SseK3 Targets Small Rab GTPases
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DOI：
10.3389/fcimb.2020.00419
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发表时间：
2020-08-19
影响因子：
5.7
通讯作者：
Giogha, Cristina
中科院分区：
文献类型：
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作者：
Gan, Jiyao;Scott, Nichollas E.;Giogha, Cristina
在感染过程中，沙门氏菌种将多种III型分泌系统（T3 SS）效应蛋白注入宿主细胞，介导入侵和随后的细胞内复制。在感染的早期阶段，沙门氏菌利用宿主胞内囊泡运输的关键调节因子，包括小GTP酶Rab 5和Rab 7，破坏宿主内吞囊泡运输并建立含沙门氏菌的空泡（SCV）。在细胞内复制的后期阶段，SCV与Rab GTP酶的相互作用不太明确。在这里，我们报告Rab 1，Rab 5和Rab 11在沙门氏菌感染的后期被SseK 3修饰，SseK 3是一种通过沙门氏菌致病岛2（SPI-2）III型分泌系统转运的N-乙酰葡萄糖胺（GlcNAc）转移酶效应子。SseK 3修饰Rab 1内74、82和111位的丝氨酸，这种修饰独立于Rab 1核苷酸结合而发生。SseK 3表现出高尔基体定位是独立的糖基转移酶活性，但Arg-GlcNAc转移酶活性所需的抑制碱性磷酸酶分泌转染细胞。虽然SseK 3在感染HeLa 229细胞期间对SEAP分泌具有适度的影响，但仅在感染RAW 264.7细胞期间过表达SseK 3时观察到IL-1和GM-CSF细胞因子分泌的抑制。我们的研究结果表明，除了靶向死亡受体信号传导，SseK 3可能通过干扰关键Rab GTP酶的活性而导致沙门氏菌感染。
During infection,Salmonellaspecies inject multiple type III secretion system (T3SS) effector proteins into host cells that mediate invasion and subsequent intracellular replication. At early stages of infection,Salmonellaexploits key regulators of host intracellular vesicle transport, including the small GTPases Rab5 and Rab7, to subvert host endocytic vesicle trafficking and establish theSalmonella-containing vacuole (SCV). At later stages of intracellular replication, interactions of the SCV with Rab GTPases are less well defined. Here we report that Rab1, Rab5, and Rab11 are modified at later stages ofSalmonellainfection by SseK3, an arginineN-acetylglucosamine (GlcNAc) transferase effector translocated via theSalmonellapathogenicity island 2 (SPI-2) type III secretion system. SseK3 modified arginines at positions 74, 82, and 111 within Rab1 and this modification occurred independently of Rab1 nucleotide binding. SseK3 exhibited Golgi localization that was independent of its glycosyltransferase activity but Arg-GlcNAc transferase activity was required for inhibition of alkaline phosphatase secretion in transfected cells. While SseK3 had a modest effect on SEAP secretion during infection of HeLa229 cells, inhibition of IL-1 and GM-CSF cytokine secretion was only observed upon over-expression of SseK3 during infection of RAW264.7 cells. Our results suggest that, in addition to targeting death receptor signaling, SseK3 may contribute toSalmonellainfection by interfering with the activity of key Rab GTPases.