title: Identification of a NIPSNAP homologue as host cell target for Salmonella virulence protein SpiC.
abstract: Salmonella enterica uses a type III secretion system encoded by SPI-2 to target specific virulence factors into the host cytosol of macrophages to inhibit the phagosomal-lysosomal maturation pathway. This ensures survival of Salmonella inside its intracellular niche, the Salmonella-containing vacuole (SCV). One such virulence factor is SpiC, which was previously shown to interfere with intracellular vesicular trafficking. In this study we have used a yeast two-hybrid assay to identify a NIPSNAP homologue as host cell target for SpiC that we have termed TassC. In vitro and in vivo co-purification of SpiC and TassC confirm the specificity of this interaction. Suppression of TassC production compensates a SpiC production deficit and allows spiC-Salmonella to survive within macrophages at levels comparable to wild-type Salmonella. We hypothesize that TassC is a host cell factor that determines vesicular trafficking in macrophages and is inactivated by Salmonella SpiC.
authors.affiliation: University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9113, USA.
authors.forename: Aaron H
authors.initials: AH
authors.lastname: Lee
authors.forename: Mahboubeh Papari
authors.initials: MP
authors.lastname: Zareei
authors.forename: Simon
authors.initials: S
authors.lastname: Daefler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002458:Cell Fractionation; D017930:Genes, Reporter; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques; D014617:Vacuoles / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C113197:NIPSNAP1 protein, human; C485133:Nipsnap1 protein, mouse; D016376:Oligonucleotides, Antisense; D011506:Proteins; D011993:Recombinant Fusion Proteins; C120280:SpiC protein, Salmonella