title: Acidic sphingomyelinase mediates entry of N. gonorrhoeae into nonphagocytic cells.
abstract: Invasion of human mucosal cells by N. gonorrhoeae via the binding to heparansulfate proteoglycan receptors is considered a crucial event of the infection. Using different human epithelial cells and primary fibroblasts, we show here an activation of the phosphatidylcholine-specific phospholipase C (PC-PLC) and acidic sphingomyelinase (ASM) by N. gonorrhoeae, resulting in the release of diacylglycerol and ceramide. Genetic and/or pharmacological blockade of ASM and PC-PLC cause inhibition of cellular invasion by N. gonorrhoeae. Complementation of ASM-deficient fibroblasts from Niemann-Pick disease patients restored N. gonorrhoeae-induced signaling and entry processes. The activation of PC-PLC and ASM, therefore, is an essential requirement for the entry of N. gonorrhoeae into distinct nonphagocytic human cell types including several epithelial cells and primary fibroblasts.
authors.affiliation: Max-Planck-Institut für Biologie, Abteilung Infektionsbiologie, Tübingen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Grassmé
authors.forename: E
authors.initials: E
authors.lastname: Gulbins
authors.forename: B
authors.initials: B
authors.lastname: Brenner
authors.forename: K
authors.initials: K
authors.lastname: Ferlinz
authors.forename: K
authors.initials: K
authors.lastname: Sandhoff
authors.forename: K
authors.initials: K
authors.lastname: Harzer
authors.forename: F
authors.initials: F
authors.lastname: Lang
authors.forename: T F
authors.initials: TF
authors.lastname: Meyer
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D003228:Conjunctiva / Q000166:cytology; D004847:Epithelial Cells / Q000382:microbiology*; D005347:Fibroblasts / Q000166:cytology / Q000382:microbiology; D006069:Gonorrhea / Q000382:microbiology*; D006801:Humans; D009344:Neisseria gonorrhoeae / Q000201:enzymology* / Q000472:pathogenicity; D009542:Niemann-Pick Diseases / Q000201:enzymology; D015398:Signal Transduction / Q000502:physiology; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D002518:Ceramides; D010738:Type C Phospholipases; D013108:Sphingomyelin Phosphodiesterase; C105598:phosphatidylcholine-specific phospholipase C