title: The virulence protein SopD2 regulates membrane dynamics of Salmonella-containing vacuoles.
abstract: Salmonella enterica serovar Typhimurium is a Gram-negative bacterial pathogen causing gastroenteritis in humans and a systemic typhoid-like illness in mice. The capacity of Salmonella to cause diseases relies on the establishment of its intracellular replication niche, a membrane-bound compartment named the Salmonella-containing vacuole (SCV). This requires the translocation of bacterial effector proteins into the host cell by type three secretion systems. Among these effectors, SifA is required for the SCV stability, the formation of Salmonella-induced filaments (SIFs) and plays an important role in the virulence of Salmonella. Here we show that the effector SopD2 is responsible for the SCV instability that triggers the cytoplasmic release of a sifA(-) mutant. Deletion of sopD2 also rescued intra-macrophagic replication and increased virulence of sifA(-) mutants in mice. Membrane tubular structures that extend from the SCV are the hallmark of Salmonella-infected cells. Until now, these unique structures have not been observed in the absence of SifA. The deletion of sopD2 in a sifA(-) mutant strain re-established membrane trafficking from the SCV and led to the formation of new membrane tubular structures, the formation of which is dependent on other Salmonella effector(s). Taken together, our data demonstrate that SopD2 inhibits the vesicular transport and the formation of tubules that extend outward from the SCV and thereby contributes to the sifA(-) associated phenotypes. These results also highlight the antagonistic roles played by SopD2 and SifA in the membrane dynamics of the vacuole, and the complex actions of SopD2, SifA, PipB2 and other unidentified effector(s) in the biogenesis and maintenance of the Salmonella replicative niche.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, CNRS UMR 6102, INSERM U631, Université de la Méditerranée, Parc Scientifique de Luminy, Marseille, France.
authors.forename: Nina
authors.initials: N
authors.lastname: Schroeder
authors.forename: Thomas
authors.initials: T
authors.lastname: Henry
authors.forename: Chantal
authors.initials: C
authors.lastname: de Chastellier
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhao
authors.forename: Aude-Agnès
authors.initials: AA
authors.lastname: Guilhon
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gorvel
authors.forename: Stéphane
authors.initials: S
authors.lastname: Méresse
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D001692:Biological Transport; D006023:Glycoproteins / Q000502:physiology; D054884:Host-Pathogen Interactions; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D012480:Salmonella Infections; D012486:Salmonella typhimurium / Q000472:pathogenicity / Q000502:physiology*; D014617:Vacuoles / Q000378:metabolism / Q000382:microbiology*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D006023:Glycoproteins; C478165:PipB2 protein, Salmonella enterica; C421862:SifA protein, Salmonella; C116105:SopD protein, Salmonella