Gardnerellavaginolysin potentiates glycan molecular mimicry byNeisseria gonorrhoeae

Abstract

AbstractBacterial vaginosis (BV) is a condition of the vaginal microbiome in which there are lower levels of “healthy”Lactobacillusspecies and an outgrowth of diverse anaerobic bacteria. BV is associated with increased risk of infection by the bacteriumNeisseria gonorrhoeae- the causative agent of gonorrhea. Here we test if one known facet of BV - the presence of bacterial cytolysins – leads to the mobilization of specific intracellular contents that aid in gonococcal virulence. We cloned and expressed recombinant vaginolysin (VLY), a cytolysin produced by the BV-associated bacteriumGardnerella, verifying that it liberates the contents of red blood cells and cervical epithelial (HeLa) cells while vector control preparations made in parallel did not. We tested if VLY mediates a well-known virulence mechanism of gonococcus – the molecular mimicry of host glycans. To evade host immunity,N. gonorrhoeaecaps its surface lipooligosaccharide (LOS) with α2-3-linked sialic acid. To do this, gonococci must scavenge an intermediate metabolite made and used inside host cells. Flow-cytometry based lectin-binding assays showed that, compared to controls, gonococci exposed to vaginolysin-liberated contents of HeLa cells displayed greater sialic acid capping of their LOS. This higher level of bacterial sialylation was accompanied by increased binding of the complement regulatory protein Factor H, and greater resistance to complement attack. Together these results suggest that cytolytic activities present during BV may enhance the ability ofN. gonorrhoeaeto capture intracellular metabolites and evade host immunity via glycan molecular mimicry.