title: Salmonella exploits Arl8B-directed kinesin activity to promote endosome tubulation and cell-to-cell transfer.
abstract: 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.
authors.affiliation: Cell Biology Program, Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Kaniuk
authors.forename: Veronica
authors.initials: V
authors.lastname: Canadien
authors.forename: Richard D
authors.initials: RD
authors.lastname: Bagshaw
authors.forename: Malina
authors.initials: M
authors.lastname: Bakowski
authors.forename: Virginie
authors.initials: V
authors.lastname: Braun
authors.forename: Marija
authors.initials: M
authors.lastname: Landekic
authors.forename: Shuvadeep
authors.initials: S
authors.lastname: Mitra
authors.forename: Ju
authors.initials: J
authors.lastname: Huang
authors.forename: Won Do
authors.initials: WD
authors.lastname: Heo
authors.forename: Tobias
authors.initials: T
authors.lastname: Meyer
authors.forename: Laurence
authors.initials: L
authors.lastname: Pelletier
authors.forename: Helene
authors.initials: H
authors.lastname: Andrews-Polymenis
authors.forename: Michael
authors.initials: M
authors.lastname: McClelland
authors.forename: Tony
authors.initials: T
authors.lastname: Pawson
authors.forename: Sergio
authors.initials: S
authors.lastname: Grinstein
authors.forename: John H
authors.initials: JH
authors.lastname: Brumell
mesh_terms: D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism* / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D012486:Salmonella typhimurium / Q000472:pathogenicity*
chemical_list: C511801:ARL8B protein, human; C488101:KIF5B protein, human; D016547:Kinesins; D020727:ADP-Ribosylation Factors