A highly conserved, inhibitable astacin metalloprotease from Teladorsagia circumcincta is required for cuticle formation and nematode development
Abstract
Parasitic nematodes cause chronic, debilitating infections in both livestock and humans worldwide, and many have developed multiple resistance to the currently available anthelmintics. The protective collagenous cuticle of these parasites is required for nematode survival and its synthesis has been studied extensively in the free-living nematode, Caenorhabditis elegans. The collagen synthesis pathway is a complex, multi-step process involving numerous key enzymes, including the astacin metalloproteases. Nematode astacinsare crucial for C. elegans development, having specific roles in hatching, moulting and cuticle synthesis. NAS-35 (also called DPY-31) is a homologue of a vertebrate procollagen C-proteinase and performs a central role in cuticle formation of C. elegans as its mutation causes temperature-sensitive lethality and cuticle defects. The characterisation of DPY-31 from the ovine gastrointestinal nematode Teladorsagia circumcincta and its ability to rescue the C. elegans mutant is described. Compounds with a hydroxamate functional group have previously been shown to be potent inhibitors of procollagen C-proteinases and were therefore examined for inhibitory activity against the T. circumcincta enzyme. Phenotypic screen...Continue Reading
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Anthelmintics
Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.
Anthelmintics (ASM)
Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.