Moulting and hatching in nematodes; the role of astacin metalloproteases as potential anti-nematode targets

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Parasitic nematodes are a major pest of plants and animals. Around 1 billion people, predominantly in the developing world, harbour parasitic nematodes that cause chronic and debilitating diseases. In addition, nematodes cause a significant economic burden to agriculture, affecting crops and livestock throughout the world. Methods to control nematodes are relatively limited, and drug resistance is becoming common. All nematodes share a common lifecycle growing from an egg through 4 immature larval stages before reaching the sexually mature adult stage. Progression from egg to larvae involves a hatching process, and from individual larval stages to adulthood involves a repeated process termed moulting, where the external skeleton is shed and a new one synthesised. The moulting process allows growth. The astacin enzymes are catalysts that are involved in the processes of hatching, skeleton synthesis and moulting. The specific roles played by this class of enzymes have been confirmed in a model experimental system and will now be examined and characterized in an important veterinary parasite. The nematode Haemonchus contortus is a common and economically significant parasite of sheep and goats. Information gained in this system will also be of relevance in other parasites of animals and plants. The project aims are to identify, study and exploit these enzymes with the overall goal of identifying vaccine and drug targets to treat and control nematode infections.