title: The Salmonella Typhimurium effector protein SopE transiently localizes to the early SCV and contributes to intracellular replication.
abstract: Salmonella enterica serovar Typhimurium (S. Tm) is a facultative intracellular pathogen that induces entry into non-phagocytic cells by a Type III secretion system (TTSS) and cognate effector proteins. Upon host cell entry, S. Tm expresses a second TTSS and subverts intracellular trafficking to create a replicative niche - the Salmonella-containing vacuole (SCV). SopE, a guanidyl exchange factor (GEF) for Rac1 and Cdc42, is translocated by the TTSS-1 upon host cell contact and promotes entry through triggering of actin-dependent ruffles. After host cell entry, the bulk of SopE undergoes proteasomal degradation. Here we show that a subfraction is however detectable on the nascent SCV membrane up to ∼ 6 h post infection. Membrane localization of SopE and the closely related SopE2 differentially depend on the Rho-GTPase-binding GEF domain, and to some extent involves also the unstructured N-terminus. SopE localizes transiently to the early SCV, dependent on continuous synthesis and secretion by the TTSS-1 during the intracellular state. Mutant strains lacking SopE or SopE2 are attenuated in early intracellular replication, while complementation restores this defect. Hence, the present study reveals an unanticipated role for SopE and SopE2 in establishing the Salmonella replicative niche, and further emphasizes the importance of entry effectors in later stages of host-cell manipulation.
authors: Institute of Microbiology, ETH Zürich, Vladimir-Prelog-Weg 4, 8093, Zürich, Switzerland.
authors: Pascale
authors: P
authors: Vonaesch
authors: Mikael E
authors: ME
authors: Sellin
authors: Steven
authors: S
authors: Cardini
authors: Vikash
authors: V
authors: Singh
authors: Manja
authors: M
authors: Barthel
authors: Wolf-Dietrich
authors: WD
authors: Hardt
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis*; D004252:DNA Mutational Analysis; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry*; D051379:Mice; D041681:NIH 3T3 Cells; D021381:Protein Transport; D012480:Salmonella Infections / Q000382:microbiology; D012486:Salmonella typhimurium / Q000254:growth & development*; D014617:Vacuoles / Q000737:chemistry* / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; C103987:SopE protein, Salmonella