Mechanisms of resistance and susceptibility to schistosome infection in Biomphalaria spp.

Schistosomiasis (a disease also known as Bilharzia) is a significant health problem in many developing countries, causing great losses in economy and man power where it prevails. In Africa, particularly south of the Sahara, the prevalence, intensity and incidence of schistosomiasis is showing no decrease and it is estimated that 85% of the 200 million people with this disease live in Africa.                                                                                                       

Schistosomiasis is caused by a parasitic trematode (also called a flatworm or fluke) of the genus Schistosoma. These parasites (known as schistosomes) have a complex life cycle that involves both an intermediate snail host in which asexual reproduction of the parasite takes place and a definitive vertebrate host (such as man) in which the parasites sexually reproduce. More information on the schistosome life cycle can be found here.

The disease is often associated with water resource development projects, such as dams and irrigation schemes, where the snail intermediate hosts of the parasite can breed. The host-parasite relationship in both the intermediate snail host and the definitive vertebrate host is complex and many questions remain to be answered regarding host-parasite interactions. We are investigating the mechanisms underlying the susceptibility and resistance of snails to infection by the schistosome parasite. An understanding of these interactions is important to aid future attempts to control schistosomiasis. One important control strategy is based on the premise that snails resistant to parasitic infection could be used as biological competitors to replace existing susceptible snails in endemic areas. This approach, however, requires a more thorough understanding of the relationship between parasites and snails. The genetics of the snails play a major role in determining the various outcomes of parasite invasion and whilst many attempts have been made to breed schistosome-resistant snails, far less is understood of the mechanisms underpinning this resistance. Our collaborator Professor Mike Doenhoff has been breeding lines of schistosome-susceptible and schistosome-resistant snails for many years resulting in excellent lineages of truly susceptible and resistant snails. We are now working together to explore the potential mechanisms underlying the phenotype of these lineages. We are using an integrative functional proteomic approach to understand the mechanisms of immune function and disease pathogenesis in the snail, combining novel proteomics technology (in particular Difference Gel Electrophoresis, DIGE) with molecular biology and immunology. Our investigations will determine the changes in the expression levels or post-translational modifications of proteins in response to schistosome challenge. This information will provide valuable insights into the factors determining the outcome of infection in resistant and susceptible snail lines and determine the changes in the expression levels of these immune related proteins or post-translational modifications of them in response to parasite challenge.