Abstract
Obligate human pathogenic Neisseria gonorrhoeae are the second most frequent bacterial cause of sexually transmitted diseases. These bacteria invade different mucosal tissues and occasionally disseminate into the bloodstream. Invasion into epithelial cells requires the activation of host cell receptors by the formation of ceramide-rich platforms. Here, we investigated the role of sphingosine in the invasion and intracellular survival of gonococci. Sphingosine exhibited an anti-gonococcal activity in vitro. We used specific sphingosine analogs and click chemistry to visualize sphingosine in infected cells. Sphingosine localized to the membrane of intracellular gonococci. Inhibitor studies and the application of a sphingosine derivative indicated that increased sphingosine levels reduced the intracellular survival of gonococci. We demonstrate here, that sphingosine can target intracellular bacteria and may therefore exert a direct bactericidal effect inside cells.
Highlights
Since the last decade, cases of bacterial sexual transmitted diseases (STDs) are rising worldwide again
Disseminated gonococcal infection is linked to the expression of the major outer membrane protein PorBIA, which facilitates the invasion of gonococci through the binding of scavenger receptor expressed on endothelial cells (SREC-I) (Rechner et al, 2007)
How downstream signaling events affect bacterial invasion, we investigated the role of sphingosine kinases (SphKs) on neisserial adherence and invasion with the laboratory strain N927 (Figures 1, 2) and the clinical isolate 24871 (Zeth et al, 2013) (Supplementary Figure 1)
Summary
Cases of bacterial sexual transmitted diseases (STDs) are rising worldwide again. Gonorrhea, the second most frequent STD with 106 million cases per year (WHO), is caused by infections with the obligate human pathogen Neisseria gonorrhoeae. Disseminated gonococcal infection is linked to the expression of the major outer membrane protein PorBIA, which facilitates the invasion of gonococci through the binding of scavenger receptor expressed on endothelial cells (SREC-I) (Rechner et al, 2007). This invasion mechanism is independent of the neisserial virulence factors type IV pili and Opa (Opacity-associated) proteins, but depends on low phosphate concentrations (Zeth et al, 2013). We have previously shown that the Intracellular Survival of Neisseria
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