The Phylogeny, Structure and Function of Trematode Cysteine Proteases, with Particular Emphasis on the Fasciola hepatica
Helminth parasites (nematodes, flatworms and cestodes) infect over 1 billion of the world’s population causing high morbidity and mortality. The large tissue-dwelling worms express papain-like cysteine peptidases, termed cathepsins that play important rol
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School of Biomedical and Health Sciences, University of Western Sydney (UWS), Narellan Road, Campbelltown, NSW, Australia; 2Institute of Parasitology, McDonald Campus, McGill University, St. Anne de Bellevue, Quebec, Canada; 3i3 Institute (IBID), University of Technology Sydney (UTS), Ultimo, Sydney, Australia *Corresponding Author: Mark W. Robinson—Email: [email protected]
Abstract:
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of the world’s population causing high morbidity and mortality. The large tissue-dwelling worms express papain-like cysteine peptidases, termed cathepsins that play important roles in virulence including host entry, tissue migration and the suppression of host immune responses. Much of our knowledge of helminth & The developmentally-regulated expression of these proteases correlates with the passage of parasites through host tissues and their encounters with different host macromolecules. Recent phylogenetic, biochemical and structural studies indicate that trematode cathepsins exhibit overlapping but distinct substrate @ an overview of the evolution, biochemistry and structure of these important enzymes and highlight how recent advances in proteomics and gene silencing techniques are allowing researchers to probe their biological functions. We focus mainly on members of the cathepsin L gene family of the animal and human pathogen, Fasciola hepatica, because of our deep understanding of their function, biochemistry and structure.
Cysteine Proteases of Pathogenic Organisms, edited by Mark W. Robinson and John P. Dalton. ©2011 Landes Bioscience and Springer Science+Business Media. 116
THE PHYLOGENY, STRUCTURE AND FUNCTION OF TREMATODE CYSTEINE
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INTRODUCTION @ @ caused by these large tissue-dwelling parasites are amongst the most prevalent on earth with over one billion people infected worldwide, predominantly in poverty-stricken regions in developing countries.1 & > important human pathogens.2 Medically important trematode genera include Schistosoma, Paragonimus, Opisthorchis, Clonorchis and Fasciola< & Schistosoma reside in the vascular system of humans and cause a disease known as Bilharzia or 250 million people in over 70 tropical countries and results in 280,000 deaths annually in sub-Saharan Africa alone and is by far the most important trematode infection.3,4 & P. westermani) or liver (C. sinensis, Opisthorchis spp.) placing 600 millon people at risk of infection across Asia.5,6" & Fasciola infect domestic animals (sheep, cattle and water buffalo) causing a disease known as fasciolosis. Although traditionally
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