Abstract
BackgroundVibrio 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.ResultsWe 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.ConclusionThis is the first report of a molecule able to inhibit the binding of VVH to target cells without oligomerization of VVH.
Highlights
Vibrio vulnificus hemolysin (VVH) is a pore-forming toxin secreted by Vibrio vulnificus
We found that cellular cholesterol is not necessary for the binding of VVH to target cells
Cholesterol contents of erythrocyte ghosts was decreased from 1.03 ± 0.1 mg/dl to 0.1 ± 0.0 mg/dl by treatment with 10 mM MβCD, whereas the VVH binding on 10 mM MβCD-treated erythrocyte ghosts was not decreased compared with that of MβCD non-treated ghost membrane (Fig. 1)
Summary
A wide variety of pathogenic bacteria, both Grampositive and Gram-negative, produce pore-forming toxins (PFTs) [1,2,3]. VVH is a PFT secreted by V. vulnificus that induces cytotoxicity against variety of cells and cell types by forming small pores on target cell membrane via oligomerization of toxin-monomer [4, 5]. Cholesterol exists in every type of cell ubiquitously and pre-incubation with cholesterol inhibited the cytotoxicity of VVH [6, 7]. For these reasons, cellular cholesterol was believed to be a good candidate cellular receptor for VVH. It is known that cholesterol induces oligomerization of VVH, and VVH oligomer loses its ability to bind. Kashimoto et al BMC Microbiology (2020) 20:69 that can inhibit the binding of VVH to the cellular membrane without oligomer formation
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