Cholesterol induce oligomerization of Vibrio vulnificus cytolysin specifically.

Byeong-Soo Kim,Jong-Suk Kim

doi:10.1038/emm.2002.33

Byeong-Soo Kim, Jong-Suk Kim

Open Access

https://doi.org/10.1038/emm.2002.33

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Abstract

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.

Highlights

The halophilic bacterium Vibrio vulnificus is known to be a life-threatening pathogen that causes septicemia and serious wound infection in human
V. vulnificus cytolysin (VVC) shows a high affinity to mammalian cell membranes, indicating that it has a broad spectrum of cytotoxicity against a variety of cells including erythrocytes, neutrophils, mast cells, endothelial cells, and macrophages (Kreger and Lockwood, 1981; Yamanaka et al, 1990; Kim et al, 1993; Park et al, 1994; Chae et al, 1996; Kim, 1997; Kim et al, 1998; Kwon et al, 2001; Kang et al, 2002)
Many papers indicate that a few of bacterial toxins are inactivated by various lipids such as phospholipids, gangliosides, and cholesterol (Takeda et al, 1975; Prigent et al, 1976; Shinoda et al, 1985)

Summary

Introduction

The halophilic bacterium Vibrio vulnificus is known to be a life-threatening pathogen that causes septicemia and serious wound infection in human. Kreger and Lockwood (1981) demonstrated that V. vulnificus cytolysin (VVC) showed hemolytic and lethal activity, and acted as vascular permeability factor. It has been known that the lysis of erythrocytes caused by VVC is colloid-osmotic in nature and that VVC, after binding to the erythrocyte membrane, oligomerize to form small pores in the membrane resulting in cell lysis (Kim et al, 1993). Cholesterol inactivates VVC by converting active monomer cytolysin into inactive oligomer, suggesting that the cytolysin lyses erythrocytes through the formation of small pores on erythrocyte membrane by cholesterol-mediated oligomerization of the cytolysin (Kim et al, 1993).

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