| Abstract [eng] |
Pore formation is a powerful and widespread mechanism used by many pathogenic bacteria to attack host cells. Vaginolysin (VLY) secreted by Gardnerella vaginalis belongs to a class of bacterial pore-forming proteins, namely cholesterol-dependent cytolysins (CDCs). VLY is thought to be responsible for the virulence of G. vaginalis by contributing to the changes in women reproductive tract microbiota. This study aimed to investigate and characterise the features of G. vaginalis toxin VLY and its pore-forming mechanism using in vitro systems. We developed an experimental system to measure the kinetics of pore formation on artificial membrane models of liposomes containing cholesterol and attached human protein CD59. Even though CD59 is not necessary for VLY pore formation, it markedly promotes this process. The interface between VLY and CD59 forms a continuous β sheet between the two proteins. CD59 enhances VLY affinity for the cell membrane and expedites the rate of pore formation. Moreover, membrane-bound CD59 can trigger VLY oligomerisation, although, without cholesterol, the oligomers cannot perforate the membrane. We advanced the experimental frontier to reveal that human protein CD59 pre concentrates VLY to enable an efficient pore formation in cholesterol-containing membranes. |
