Invasion of human mucosal cells by N. gonorrhoeae via the binding to h
eparansulfate proteoglycan receptors is considered a crucial event of
the infection. Using different human epithelial cells and primary fibr
oblasts, we show here an activation of the phosphatidylcholine-specifi
c phospholipase C (PC-PLC) and acidic sphingomyelinase (ASM) by N. gon
orrhoeae, resulting in the release of diacylglycerol and ceramide. Gen
etic and/or pharmacological blockade of ASM and PC-PLC cause inhibitio
n of cellular invasion by N. gonorrhoeae. Complementation of ASM-defic
ient fibroblasts from Niemann-Pick disease patients restored N. gonorr
hoeae-induced signaling and entry processes. The activation of PC-PLC
and ASM, therefore, is an essential requirement for the entry of N. go
norrhoeae into distinct nonphagocytic human cell types including sever
al epithelial cells and primary fibroblasts.