title: PERP, a host tetraspanning membrane protein, is required for Salmonella-induced inflammation.
abstract: Salmonella enterica Typhimurium induces intestinal inflammation through the activity of type III secreted effector (T3SE) proteins. Our prior results indicate that the secretion of the T3SE SipA and the ability of SipA to induce epithelial cell responses that lead to induction of polymorphonuclear transepithelial migration are not coupled to its direct delivery into epithelial cells from Salmonella. We therefore tested the hypothesis that SipA interacts with a membrane protein located at the apical surface of intestinal epithelial cells. Employing a split ubiquitin yeast-two-hybrid screen, we identified the tetraspanning membrane protein, p53 effector related to PMP-22 (PERP), as a SipA binding partner. SipA and PERP appear to have intersecting activities as we found PERP to be involved in proinflammatory pathways shown to be regulated by SipA. In sum, our studies reveal a critical role for PERP in the pathogenesis of S. Typhimurium, and for the first time demonstrate that SipA, a T3SE protein, can engage a host protein at the epithelial surface.
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Kelly N
authors.initials: KN
authors.lastname: Hallstrom
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: C V
authors.initials: CV
authors.lastname: Srikanth
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Terence A
authors.initials: TA
authors.lastname: Agbor
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dumont
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Kristen N
authors.initials: KN
authors.lastname: Peters
authors.affiliation: Eye and Vision Science Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.
authors.forename: Luminita
authors.initials: L
authors.lastname: Paraoan
authors.affiliation: Department of Cell Biology, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Casanova
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Boll
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Beth A
authors.initials: BA
authors.lastname: McCormick
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D016147:Genes, Tumor Suppressor; D054884:Host-Pathogen Interactions; D006801:Humans; D007249:Inflammation / Q000382:microbiology* / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D012486:Salmonella typhimurium / Q000276:immunology*; D057705:Transendothelial and Transepithelial Migration; D020798:Two-Hybrid System Techniques
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; C416404:PERP protein, human; C118287:SipA protein, Salmonella