CHARACTERIZATION OF THE ROLE OF CERCARIAL ELASTASE IN SCHISTOSOME HOST INVASION AND IMMUNE EVASION

Schistosomes and related blood flukes are platyhelminth (flatworm) parasites ofhosts ranging from fish to humans. Cercarial elastase is an evolutionarily distinctserine protease that is essential for invasion of human skin by the larva ofSchistosoma mansoni. Several isoforms of the protease exist, but little is knownabout their genomic organization and regulation. Previous work suggests that the protease is able to degrade a variety of host macromolecules, including dermal and immune components. The expansion of the gene family and the indication that various protease isoforms had different substrate specificities presents two alternative evolutionary scenarios: that gene duplication had allowed for differential regulation and diversified substrate specificity, in order to facilitate multiple functions in host invasion; or that SmCE gene duplication directly enhanced fitness by simply increasing the amount of protease present. Work presented as part of this thesis project indicates that expansion of the cercarial elastase gene family is an example of gene dosage. In addition, work in other schistosomes species, including those that infect humans and those that are avian-specific, suggest that different schistosome lineages have evolved to use different classes of proteases in cercarial invasion