Vibrio vulnificus cytolysin (VVC) has been implicated as one of the important virulence determinants of V. vulnificus that causes serious septicemia and wound infection. An attempt was made to investigate that VVC could act as a ligand which stimulates intracellular signaling systems. Cholesterol dose-dependently blocked VVC hemolytic activity through oli-gomerization of cytolysin. Among cholesterol derivatives including 7-dehydrocholesterol, cholesteryl esters, deoxycholate, and cholestane tested, only 7-dehydrocholesterol induced oligomerization as well as inactivation of VVC. These results show that oligomerization of VVC is completely dependent on three-dimensional structure of cholesterol where specific interaction of cholesterol at oligomerization sites of VVC is very selective. These findings support the idea that cholesterol which constitute many of cellular plasma membrane could be a receptor of VVC on plasma membrane of target cells.
Animals ; Bacterial Toxins/antagonists & inhibitors/chemistry/metabolism ; Cholesterol/chemistry/*pharmacology ; Cytotoxins/antagonists & inhibitors/*chemistry/*metabolism ; Dehydrocholesterols/chemistry/pharmacology ; Dose-Response Relationship, Drug ; Erythrocytes/drug effects ; Hemolysis/drug effects ; Mice ; Molecular Structure ; Signal Transduction ; Substrate Specificity ; Vibrio/*chemistry