title: Neutral sphingomyelinase 2 is a key factor for PorB-dependent invasion of Neisseria gonorrhoeae.
abstract: Disseminated gonococcal infection (DGI) is a rare but serious complication caused by the spread of Neisseria gonorrhoeae in the human host. Gonococci associated with DGI mainly express the outer membrane protein PorBIA that binds to the scavenger receptor expressed on endothelial cells (SREC-I) and mediates bacterial uptake. We recently demonstrated that this interaction relies on intact membrane rafts that acquire SREC-I upon attachment of gonococci and initiates the signalling cascade that finally leads to the uptake of gonococci in epithelial cells. In this study, we analysed the role of sphingomyelinases and their breakdown product ceramide. Gonococcal infection induced increased levels of ceramide that was enriched at bacterial attachment sites. Interestingly, neutral but not acid sphingomyelinase was mandatory for PorBIA -mediated invasion into host cells. Neutral sphingomyelinase was required to recruit the PI3 kinase to caveolin and thereby activates the PI3 kinase-dependent downstream signalling leading to bacterial uptake. Thus, this study elucidates the initial signalling processes of bacterial invasion during DGI and demonstrates a novel role for neutral sphingomyelinase in the course of bacterial infections.
authors.affiliation: Department of Microbiology, University of Würzburg Biocenter, Würzburg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Faulstich
authors.forename: Franziska
authors.initials: F
authors.lastname: Hagen
authors.forename: Elita
authors.initials: E
authors.lastname: Avota
authors.forename: Vera
authors.initials: V
authors.lastname: Kozjak-Pavlovic
authors.forename: Ann-Cathrin
authors.initials: AC
authors.lastname: Winkler
authors.forename: Yibo
authors.initials: Y
authors.lastname: Xian
authors.forename: Sibylle
authors.initials: S
authors.lastname: Schneider-Schaulies
authors.forename: Thomas
authors.initials: T
authors.lastname: Rudel
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D004705:Endocytosis; D054884:Host-Pathogen Interactions; D006801:Humans; D009344:Neisseria gonorrhoeae / Q000502:physiology*; D018272:Porins / Q000378:metabolism*; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*
chemical_list: D002518:Ceramides; D018272:Porins; C057699:porin protein, Neisseria; D013108:Sphingomyelin Phosphodiesterase