title: Biomphalysin, a new β pore-forming toxin involved in Biomphalaria glabrata immune defense against Schistosoma mansoni.
abstract: Aerolysins are virulence factors belonging to the β pore-forming toxin (β-PFT) superfamily that are abundantly distributed in bacteria. More rarely, β-PFTs have been described in eukaryotic organisms. Recently, we identified a putative cytolytic protein in the snail, Biomphalaria glabrata, whose primary structural features suggest that it could belong to this β-PFT superfamily. In the present paper, we report the molecular cloning and functional characterization of this protein, which we call Biomphalysin, and demonstrate that it is indeed a new eukaryotic β-PFT. We show that, despite weak sequence similarities with aerolysins, Biomphalysin shares a common architecture with proteins belonging to this superfamily. A phylogenetic approach revealed that the gene encoding Biomphalysin could have resulted from horizontal transfer. Its expression is restricted to immune-competent cells and is not induced by parasite challenge. Recombinant Biomphalysin showed hemolytic activity that was greatly enhanced by the plasma compartment of B. glabrata. We further demonstrated that Biomphalysin with plasma is highly toxic toward Schistosoma mansoni sporocysts. Using in vitro binding assays in conjunction with Western blot and immunocytochemistry analyses, we also showed that Biomphalysin binds to parasite membranes. Finally, we showed that, in contrast to what has been reported for most other members of the family, lytic activity of Biomphalysin is not dependent on proteolytic processing. These results provide the first functional description of a mollusk immune effector protein involved in killing S. mansoni.
authors.affiliation: CNRS, UMR 5244, Ecologie et Evolution des Interactions, Perpignan, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Galinier
authors.forename: Julien
authors.initials: J
authors.lastname: Portela
authors.forename: Yves
authors.initials: Y
authors.lastname: Moné
authors.forename: Jean François
authors.initials: JF
authors.lastname: Allienne
authors.forename: Hélène
authors.initials: H
authors.lastname: Henri
authors.forename: Stéphane
authors.initials: S
authors.lastname: Delbecq
authors.forename: Guillaume
authors.initials: G
authors.lastname: Mitta
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gourbal
authors.forename: David
authors.initials: D
authors.lastname: Duval
mesh_terms: D000818:Animals; D001700:Biomphalaria / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D003001:Cloning, Molecular; D006374:Helminthiasis, Animal / Q000276:immunology* / Q000378:metabolism; D006790:Host-Parasite Interactions; D052899:Pore Forming Cytotoxic Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D012550:Schistosoma mansoni / Q000302:isolation & purification / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000378:metabolism; D037521:Virulence Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D052899:Pore Forming Cytotoxic Proteins; D037521:Virulence Factors; C583769:biomphalysin protein, Biomphalaria glabrata
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