Biomphalysin, a New β Pore-forming Toxin Involved in Biomphalaria glabrata Immune Defense against Schistosoma mansoni

PLoS Pathogens

David Duval¹  Benjamin Gourbal²  Hélène Henri³  Richard Galinier³  Yves Moné³  Guillaume Mitta⁴  Jean François Allienne⁵  Julien Portela⁵  Stéphane Delbecq⁵ 

[1] CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Villeurbanne, France;Université Lyon 1;CNRS, UMR 5244, Ecologie et Evolution des Interactions (2EI), Perpignan, France;Université de Lyon, Lyon;Université de Perpignan Via Domitia, Perpignan, France

关键词: Sporocysts;    Schistosoma mansoni;    Toxins;    Protein structure prediction;    Sequence motif analysis;    Parasitic diseases;    Phylogenetic analysis;    Polymerase chain reaction;   

DOI  :  10.1371/journal.ppat.1003216

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY