沙门氏菌抑制了曼诺-6-酸盐受体的逆向贩运和溶酶体功能
Kieran McGourty1, Teresa L Thurston, Sophie A Matthews
1Section of Microbiology, Centre for Molecular Microbiology and Infection, Imperial College London, Armstrong Road, London SW7 2AZ, UK.
概括
沙门氏菌 (Salmonella enterica) 使用效应器SifA通过干扰-6-酸盐受体 (MPR) 贩运来破坏宿主细胞溶解体功能. 这种细菌策略通过减少 lysosomal 活动来增强沙门氏菌的生长.
科学领域:
- 微生物学 微生物学
- 细胞生物学 细胞生物学
- 病原体与宿主之间的相互作用
背景情况:
- 沙门氏菌 (Salmonella enterica) 是一种在真空中复制的细胞内病原体.
- 沙门氏菌真空体表现出 lysosomal 特性,但降低了水解酶含量.
- 曼诺-6酸盐受体 (MPR) 对于溶酶体酶运输至关重要.
研究的目的:
- 研究沙门氏菌效应剂SifA影响宿主细胞 lysosome 功能的机制.
- 确定SifA-SKIP/PLEKHM2相互作用在MPR贩运中的作用.
- 为了阐明沙门氏菌是如何操纵宿主细胞转运通路进行复制的.
主要方法:
- 研究了沙门氏菌效应剂SifA与宿主细胞蛋白SKIP/PLEKHM2.2之间的相互作用.
- 分析了SifA对Rab9依赖的MPR逆向贩运的影响.
- 评估了具有调节 lysosomal 活动的宿主细胞中的沙门氏菌生长.
主要成果:
- SifA与SKIP/PLEKHM2结合,颠覆了Rab9依赖的MPR逆向流通,并减弱了溶酶体的功能.
- 在受感染的细胞中,SifA与SKIP和Rab9形成稳定的复合体,将Rab9.9隔离.
- 在 lysosomal 活性降低的细胞中,沙门氏菌的生长会增强,而在活性较高的细胞中则会减少.
结论:
- 沙门氏菌真空体与宿主细胞溶解体融合,其功效被SifA降低.
- 通过SifA中介破坏MPR贩运是沙门氏菌病原的关键机制.
- 准宿主细胞逆行运输是一种保存的细菌策略,用于细胞内复制.
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