Institute of Infection and Immunity, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China.
Commun Biol. 2020 Jun 5;3(1):287. doi: 10.1038/s42003-020-1005-2.
Salmonella enterica serovar Typhimurium, an intracellular Gram-negative bacterial pathogen, employs two type III secretion systems to deliver virulence effector proteins to host cells. One such effector, SseK3, is a Golgi-targeting arginine GlcNAc transferase. Here, we show that SseK3 colocalizes with cis-Golgi via lipid binding. Arg-GlcNAc-omics profiling reveals that SseK3 modifies Rab1 and some phylogenetically related Rab GTPases. These modifications are dependent on C-termini of Rabs but independent of the GTP- or GDP-bound forms. Arginine GlcNAcylation occurs in the switch II region and the third α-helix and severely disturbs the function of Rab1. The arginine GlcNAc transferase activity of SseK3 is required for the replication of Salmonella in RAW264.7 macrophages and bacterial virulence in the mouse model of Salmonella infection. Therefore, this SseK3 mechanism of action represents a new understanding of the strategy adopted by Salmonella to target host trafficking systems.
鼠伤寒沙门氏菌血清型 Typhimurium 是一种细胞内革兰氏阴性细菌病原体，它利用两种 III 型分泌系统将毒力效应蛋白输送到宿主细胞。其中一种效应蛋白 SseK3 是一种高尔基体靶向的精氨酸 GlcNAc 转移酶。在这里，我们表明 SseK3 通过脂质结合与顺式高尔基体共定位。Arg-GlcNAc-omics 分析显示，SseK3 修饰 Rab1 和一些系统发育上相关的 Rab GTPase。这些修饰依赖于 Rab 的 C 末端，但不依赖于 GTP 或 GDP 结合形式。精氨酸 GlcNAc 化发生在开关 II 区和第三个α螺旋中，并严重扰乱 Rab1 的功能。SseK3 的精氨酸 GlcNAc 转移酶活性是沙门氏菌在 RAW264.7 巨噬细胞中复制和沙门氏菌感染小鼠模型中细菌毒力所必需的。因此，这种 SseK3 的作用机制代表了对沙门氏菌靶向宿主运输系统所采用策略的新认识。
