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Characterization of the roles of leishmanolysin and venom-allergen-like proteins during the infection of Biomphalaria glabrata by Schistosoma mansoni
- Author / Creator
- Kabore, Alethe L.
Among the world’s most significantly neglected diseases is schistosomiasis, estimated to have infected over 261 million disadvantaged people in the tropics, and placing an additional 800 million people at risk (McManus, 2012; WHO, 2015). Despite recent international efforts to eliminate schistosomiasis through extensive expansion of drug therapy programs, it remains entrenched in many developing countries, particularly in Africa, where an estimated 280,000 people die from complications related to the disease each year (Cioli, Pica-Mattoccia, Basso, & Guidi, 2014). Schistosomiasis is unusual among human diseases in that it relies upon freshwater snails for larval development and production of the human infectious developmental stage that penetrates an individual’s skin when the parasite is encountered in infested water. Little is understood about the determinants of this snail-schistosome association, but perhaps the most essential observation to date is that not all snails can serve as suitable hosts for all given species of schistosomes. This leads naturally to investigations of what the underpinning factors of specificity are, and how they dictate infection establishment and maintenance. Much of our current understanding in this regard stems from studies that have focused on the snail immune response to the invading parasite. We know almost nothing however about how the schistosome facilitates infection. This gap in our understanding of the intermediate host infection process is the focus of my thesis work. I aimed to investigate two factors produced by Schistosoma mansoni (S. mansoni) during the infection of its natural snail host Biomphalaria glabrata (B. glabrata). Both molecules (S. mansoni leishmanolysin [SmLeish] and venom-allergen-like 3 [SmVAL3]) were chosen for in depth analysis because they possessed significant amino acid similarity to factors known to interfere with host immune responses in other host-parasite systems. Assessment of the expression of these transcripts indicated that they were expressed by S. mansoni early during the infection of B. glabrata. In order to characterize the process by which SmLeish and SmVAL3 influenced infection outcome, I generated recombinant versions of each protein along with polyclonal antibodies to facilitate detection of the native proteins. SmLeish was found to be generated as a pro-peptide that could be either secreted or cleaved from the surface of a larval schistosome. Functionally, it was found to interfere with the migration of B. glabrata immune cells. In addition, when knocked down in the free-swimming miracidial stage of the parasite using RNA interference, it was demonstrated to have an influence on infection outcome. These results together suggest that SmLeish plays a role in S. mansoni infection establishment in B. glabrata by impeding the proper functioning of the snail immune cells at the site of early schistosome penetration. This is also the first report of a schistosome-specific factor having clearly demonstrable impact on larval infection success.
- Graduation date
- Type of Item
- Master of Science
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