Open AccessPERP, a host tetraspanning membrane protein, is required for S almonella ‐induced inflammation
Author(s) -
Hallstrom Kelly N.,
Srikanth C. V.,
Agbor Terence A.,
Dumont Christopher M.,
Peters Kristen N.,
Paraoan Luminita,
Casanova James E.,
Boll Erik J.,
McCormick Beth A.
Publication year - 2015
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12406
Subject(s) - effector , biology , microbiology and biotechnology , secretion , proinflammatory cytokine , salmonella enterica , inflammation , salmonella , immunology , bacteria , biochemistry , genetics
Summary S almonella enterica T yphimurium 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 S almonella . 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 . T yphimurium, and for the first time demonstrate that SipA , a T3SE protein, can engage a host protein at the epithelial surface.