Abstract
Bilharzia is a disease affecting 230 million people worldwide (source WHO). This parasitosis is caused by schistosome, a parasitic flatworm, and in particular by Schistosoma mansoni, responsible for intestinal bilharzia in Africa and tropical America. Before entering the human body through the skin, this parasite develops in a freshwater snail, Biomphalaria glabrata, which serves as an intermediate host. In this context, we have identified and studied two proteins belonging to the pore forming toxins (PFTs) family, which we have called Biomphalysin and Glabralysin. Pore forming toxins are effectors well known in the prokaryotic world to promote their pathogenicity. These proteins are produced in a soluble way by organisms, to bind and aggregate on the target cell membranes, resulting in the creation of a lytic pore. This protein superfamily is divided into two families, alpha and beta, classified according to the pore formation modality. Previous studies have characterized for the first time §-PFTs in the mollusc Biomphalaria glabrata, these proteins have shown a key role in the immunity of the mollusc, including the ability to bind and kill the parasite. This discovery may have opened the field to the investigation of similar proteins in the mollusc and in the parasite with which it interacts. This thesis project aims, through genomic, transcriptomic and proteomic studies, to characterize and understand the function of different "pore forming toxins" present in the mollusc Biomphalaria glabrata and in the parasite Schistosoma mansoni. Thanks to data collected before and during the thesis project, we were able to characterize 23 variants related to the Biomphalysin family. This multigenic family, without intron, seems to have been acquired through horizontal gene transfer. By homology with the Biomphalysins, we were able to characterize 5 genes coding for a second group of §-PFT in Biomphalaria glabrata, which we called Glabralysins. These proteins constitute a family in their own right, close to the Cry toxins of Bacillus thuringiensis, and which structurally share homologies with the Biomphalysin. They are indeed produced by the immune cells of the mollusc and induced during the infection by the parasite Schistosoma mansoni. Finally, we were also able to discover two genes coding for toxins, called Schistolysins, of the §-PFT family in the parasite Schistosoma mansoni. These proteins seem to be widespread in parasites and play essential roles in their development, in reproduction and hypothetically in nutrition. We show that these proteins are found exclusively in the adult stage of the parasite and should therefore play a role in the interaction with the human host or in the implantation or exploitation of this host. These different approaches, in the context of the interaction between the host and its parasite, will potentially lead to the identification of new strategies for the control or management of the disease in the field. The results generated in this work could also allow to study the role of these molecules in the interaction with other pathogens or their link with other pathologies and more particularly their use in the development of new cancer treatments for example.