title: Remodelling of the actin cytoskeleton is essential for replication of intravacuolar Salmonella.
abstract: Maturation and maintenance of the intracellular vacuole in which Salmonella replicates is controlled by virulence proteins including the type III secretion system encoded by Salmonella pathogenicity island 2 (SPI-2). Here, we show that, several hours after bacterial uptake into different host cell types, Salmonella induces the formation of an F-actin meshwork around bacterial vacuoles. This structure is assembled de novo from the cellular G-actin pool in close proximity to the Salmonella vacuolar membrane. We demonstrate that the phenomenon does not require the Inv/Spa type III secretion system or cognate effector proteins, which induce actin polymerization during bacterial invasion, but does require a functional SPI-2 type III secretion system, which plays an important role in intracellular replication and systemic infection in mice. Treatment with actin-depolymerizing agents significantly inhibited intramacrophage replication of wild-type Salmonella typhimurium. Furthermore, after this treatment, wild-type bacteria were released into the host cell cytoplasm, whereas SPI-2 mutant bacteria remained within vacuoles. We conclude that actin assembly plays an important role in the establishment of an intracellular niche that sustains bacterial growth.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS-Univ.Med., Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France.
authors.forename: S
authors.initials: S
authors.lastname: Méresse
authors.forename: K E
authors.initials: KE
authors.lastname: Unsworth
authors.forename: A
authors.initials: A
authors.lastname: Habermann
authors.forename: G
authors.initials: G
authors.lastname: Griffiths
authors.forename: F
authors.initials: F
authors.lastname: Fang
authors.forename: M J
authors.initials: MJ
authors.lastname: Martínez-Lorenzo
authors.forename: S R
authors.initials: SR
authors.lastname: Waterman
authors.forename: J P
authors.initials: JP
authors.lastname: Gorvel
authors.forename: D W
authors.initials: DW
authors.lastname: Holden
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002455:Cell Division; D003599:Cytoskeleton / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D012486:Salmonella typhimurium / Q000166:cytology / Q000472:pathogenicity*; D014617:Vacuoles / Q000382:microbiology*
chemical_list: D000199:Actins