Vaginolysin (VLY)

Vaginolysin (VLY) is a pore-forming toxin produced by Gardnerella vaginalis, a bacterium central to the pathogenesis of bacterial vaginosis (BV) [1, 4]. As a member of the cholesterol-dependent cytolysin (CDC) family, VLY is distinguished by its human-specific activity, which is mediated through high-affinity binding to the human complement regulatory protein CD59 (hCD59) and membrane cholesterol [2, 5, 12]. Following receptor binding, VLY monomers undergo a conformational change and oligomerize to form large aqueous pores in the host cell membrane, leading to osmotic lysis of vaginal epithelial cells and erythrocytes [2, 3, 4]. At sublytic concentrations, VLY induces membrane blebbing and activates proinflammatory signaling cascades, including the p38 mitogen-activated protein kinase (MAPK) pathway and the production of interleukin-8 (IL-8) [1, 9, 14]. These processes contribute to the mucosal inflammation and epithelial barrier disruption characteristic of BV, which increases the risk of preterm birth and the acquisition of sexually transmitted infections like HIV [4, 11, 16]. Consequently, VLY is a primary therapeutic target, with research exploring neutralizing antibodies, toxoids, and receptor-blocking strategies to mitigate its virulence and improve clinical outcomes in BV [6, 11, 18].

Other names

Gardnerella vaginalis hemolysinGardnerella vaginalis cytolysinG. vaginalis hemolysinVLY toxin

Vaginolysin binds to human CD59 and membrane cholesterol, leading to the oligomerization of monomers into a prepore complex that subsequently inserts into the host cell membrane to form a large aqueous pore, causing cell lysis or sublytic signaling [2, 12, 15].