Vibiro vulnificus hemolysin associates with gangliosides

Abstract

Background: Vibrio vulnificus hemolysin (VVH) is a pore-forming toxin secreted by Vibrio vulnificus. Cellular cholesterol was believed to be the receptor for VVH, because cholesterol could bind to VVH and preincubation with cholesterol inhibited cytotoxicity. It has been reported that specific glycans such as N-acetyl-D-galactosamine and N-acetyl-D-lactosamine bind to VVH, however, it has not been known whether these glycans could inhibit the cytotoxicity of VVH without oligomer formation. Thus, to date, binding mechanisms of VVH to cellular membrane, including specific receptors have not been elucidated. Results: We show here that VVH associates with ganglioside GM1a, Fucosyl-GM1, GD1a, GT1c, and GD1b by glycan array. Among them, GM1a could pulldown VVH. Moreover, the GD1a inhibited the cytotoxicity of VVH without the formation of oligomers. Conclusion: This is the first report of a molecule able to inhibit the binding of VVH to target cells without oligomerization of VVH.

Vibrio vulnificus Hemolysin: Biological Activity, Regulation of vvhA Expression, and Role in Pathogenesis

“…Cholesterol is well known for its ability to inactivate the VVH through oligomerization of the toxin monomer (29). However, there are some reports that the VVH recognizes and binds to certain kinds of carbohydrates (38,39), which suggested that cellular cholesterol is not a receptor for VVH. It may be a trigger factor of conformational changes from membrane bound form to pore-form (39).…”

“…However, there are some reports that the VVH recognizes and binds to certain kinds of carbohydrates (38,39), which suggested that cellular cholesterol is not a receptor for VVH. It may be a trigger factor of conformational changes from membrane bound form to pore-form (39). Moreover, although two studies indicate VVH induces cell death via lipid raft-mediated signaling pathway in human intestinal epithelial cells (31,32), there is no evidence that the VVH localizes at lipid raft so far.…”

“…IscR activates vvhBA by relieving H-NS repression by sensing nitrosative stress (46). Meanwhile, a repressive interaction of H-NS would be relieved in response to the increase in temperature (39,49). LuxO is a central response regulator of the QS circuit in V. vulnificus, which negatively regulates vvhA expression via SmcR and HlyU (42,43).…”