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Resistance as a tool for discovering and understanding targets in parasite neuromusculature

Published online by Cambridge University Press:  29 March 2006

N. C. SANGSTER ,
J. SONG  and
J. DEMELER
N. C. SANGSTER
Affiliation:
Faculty of Veterinary Science, University of Sydney, 2006, Australia
J. SONG
Affiliation:
Faculty of Veterinary Science, University of Sydney, 2006, Australia
J. DEMELER
Affiliation:
Faculty of Veterinary Science, University of Sydney, 2006, Australia
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Abstract

The problem of anthelmintic resistance prevents efficient control of parasites of livestock and may soon compromise human parasite control. Research into the mechanisms of resistance and the quest for diagnostic tools to aid control has required research that focuses on field resistance. On the other hand, resistant worms, including those kept in the laboratory, provide useful tools for studying drug action, especially at neuromuscular targets in worms. While the needs and directions of these research aims overlap, this review concentrates on research on drug targets. In this context, resistance is a useful tool for site of action confirmation. For example, correlations between molecular expression studies and resistance assays conducted on whole worms can strengthen claims for sites of anthelmintic action. Model systems such as Caenorhabditis elegans have been very useful in understanding targets but give a limited picture as it is now clear that resistance mechanisms in this worm are different from those in parasites. Accordingly, research on parasites themselves must also be performed. Resistant isolates of the sheep nematode parasite Haemonchus contortus are the most widely used for this purpose as in vivo, in vitro, physiological and molecular studies can be performed with this species. Neuromuscular target sites for the anthelmintics levamisole and ivermectin are the best studied and have benefited most from the use of resistant worm isolates. Resistance to praziquantel and the newer chemical groups should provide new tools to explore targets in the future.

Keywords

Anthelmintic resistancelevamisoleivermectinHaemonchus contortusneuromusculature
Type
Research Article
Information
Parasitology , Volume 131 , Supplement S1: Parasite neuromusculature and its utility as a drug target , October 2005 , pp. S179 - S190
Copyright
2005 Cambridge University Press

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