Open AccessNeutral sphingomyelinase 2 is a key factor for P or B ‐dependent invasion of N eisseria gonorrhoeae
Author(s) -
Faulstich Michaela,
Hagen Franziska,
Avota Elita,
KozjakPavlovic Vera,
Winkler AnnCathrin,
Xian Yibo,
SchneiderSchaulies Sibylle,
Rudel Thomas
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.12361
Subject(s) - sphingomyelin , ceramide , neisseria gonorrhoeae , biology , microbiology and biotechnology , kinase , acid sphingomyelinase , bacterial outer membrane , downregulation and upregulation , biochemistry , membrane , apoptosis , gene , escherichia coli
Summary Disseminated gonococcal infection ( DGI ) is a rare but serious complication caused by the spread of N eisseria gonorrhoeae in the human host. Gonococci associated with DGI mainly express the outer membrane protein PorB IA 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 PorB IA ‐mediated invasion into host cells. Neutral sphingomyelinase was required to recruit the PI 3 kinase to caveolin and thereby activates the PI 3 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.