Salmonella exploits Arl8B-directed kinesin activity to promote endosome tubulation and cell-to-cell transfer
Salmonella exploits Arl8B-directed kinesin activity to promote endosome tubulation and cell-to-cell transfer
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DOI：
10.1111/j.1462-5822.2011.01663.x
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发表时间：
2011-11-01
影响因子：
3.4
通讯作者：
Brumell, John H.
中科院分区：
文献类型：
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作者：
Kaniuk, Natalia A.;Canadien, Veronica;Brumell, John H.
鼠伤寒沙门氏菌的兼性胞内病原体在宿主细胞中建立了一个复制生态位，即含沙门氏菌的空泡(SCV)。在这里，我们证明了这些细菌在感染过程中利用了Arf家族GTP酶Ar18B的功能。感染后，Ar18B定位于SCV和沿宿主细胞质微管延伸的管状内小体。Ar18B+小管部分与LAMP1和SCAMP3共定位。LAMP1+小管的形成(沙门氏菌诱导的细丝表型；SIF)需要Ar18B的表达。已知Sifs的形成需要Kinesin-1的活性。我们发现Ar18B对于激动素-1在SCV中的募集是必需的。我们之前已经证明，SCV在感染后24小时经历离心式移动到细胞外围，并经历细胞间转移来感染邻近细胞，并且这两种表型都需要Kinesin-1活性。在这里，我们证明了Ar18B是SCV在感染后24小时迁移到细胞外围以及细菌在细胞之间转移到邻近细胞所必需的。这些结果揭示了鼠伤寒沙门氏菌所选择的一种新的宿主因子，以操纵宿主的内吞途径并促进感染在宿主内的传播。
The facultative intracellular pathogen Salmonella enterica serovar Typhimurium establishes a replicative niche, the Salmonella-containing vacuole (SCV), in host cells. Here we demonstrate that these bacteria exploit the function of Arl8B, an Arf family GTPase, during infection. Following infection, Arl8B localized to SCVs and to tubulated endosomes that extended along microtubules in the host cell cytoplasm. Arl8B+ tubules partially colocalized with LAMP1 and SCAMP3. Formation of LAMP1+ tubules (the Salmonella-induced filaments phenotype; SIFs) required Arl8B expression. SIFs formation is known to require the activity of kinesin-1. Here we find that Arl8B is required for kinesin-1 recruitment to SCVs. We have previously shown that SCVs undergo centrifugal movement to the cell periphery at 24 h post infection and undergo cell-to-cell transfer to infect neighbouring cells, and that both phenotypes require kinesin-1 activity. Here we demonstrate that Arl8B is required for migration of the SCV to the cell periphery 24 h after infection and for cell-to-cell transfer of bacteria to neighbouring cells. These results reveal a novel host factor co-opted by S. Typhimurium to manipulate the host endocytic pathway and to promote the spread of infection within a host.