Acidic sphingomyelinase mediates entry of N. gonorrhoeae into nonphagocytic cells.
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.
Grassmé
H
H
Max-Planck-Institut für Biologie, Abteilung Infektionsbiologie, Tübingen, Germany.
Gulbins
E
E
Brenner
B
B
Ferlinz
K
K
Sandhoff
K
K
Harzer
K
K
Lang
F
F
Meyer
T F
TF
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
D001426:Bacterial Proteins; D002518:Ceramides; D010738:Type C Phospholipases; D013108:Sphingomyelin Phosphodiesterase; C105598:phosphatidylcholine-specific phospholipase C