Gardnerella
vaginalis produces cytolysin
vaginolysin (VLY), which has been suggested to be a contributor to bacterial
vaginosis pathogenesis. VLY along with intermedilysin (ILY) from Streptococcus intermedius have been attributed to a group of
cholesterol-dependent cytolysins (CDCs) whose pore-forming activity depends on
human CD59 (hCD59). Here, we show that different types of cells lacking hCD59
are susceptible to VLY-mediated lysis, albeit to different extents. We analyze
the effects of both hCD59 and cholesterol on VLY cytolytic activity. We show
that VLY binds to cholesterol-rich membranes of non-human cells, while VLY with
an impaired cholesterol recognition site retains binding to the
hCD59-containing cells. We further demonstrate that cholesterol binding by VLY
is sufficient to trigger the formation of oligomeric complexes on cholesterol
rich-liposomes lacking hCD59. Thus, VLY may induce cell lysis following two
alternative pathways. One requires only cholesterol and does not depend on
hCD59. The second pathway involves hCD59 contribution similarly to ILY. Apparently, under physiological conditions VLY acts in the
most effective way by accepting the assistance of hCD59.