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Nematode ligand-gated chloride channels: an appraisal of their involvement in macrocyclic lactone resistance and prospects for developing molecular markers

Published online by Cambridge University Press:  03 July 2007

S. McCAVERA ,
T. K. WALSH  and
A. J. WOLSTENHOLME
S. McCAVERA
Affiliation:
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
T. K. WALSH
Affiliation:
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
A. J. WOLSTENHOLME*
Affiliation:
Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
*
*Corresponding author. Tel: +44 1225 386553. Fax: +44 1225 386779. E-mail: [email protected]
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Summary

Ligand-gated chloride channels, including the glutamate-(GluCl) and GABA-gated channels, are the targets of the macrocyclic lactone (ML) family of anthelmintics. Changes in the sequence and expression of these channels can cause resistance to the ML in laboratory models, such as Caenorhabditis elegans and Drosophila melanogaster. Mutations in multiple GluCl subunit genes are required for high-level ML resistance in C. elegans, and this can be influenced by additional mutations in gap junction and amphid genes. Parasitic nematodes have a different complement of channel subunit genes from C. elegans, but a few genes, including avr-14, are widely present. A polymorphism in an avr-14 orthologue, which makes the subunit less sensitive to ivermectin and glutamate, has been identified in Cooperia oncophora, and polymorphisms in several subunits have been reported from resistant isolates of Haemonchus contortus. This has led to suggestions that ML resistance may be polygenic. Possible reasons for this, and its consequences for the development of molecular tests for resistance, are explored.

Keywords

Avermectinmoxidectinglutamate-gated chloride channelGABA receptorHaemonchus contortussingle nucleotide polymorphism
Type
Research Article
Information
Parasitology , Volume 134 , Special Issue 8: MARKERS FOR ANTHELMINTIC RESISTANCE , August 2007 , pp. 1111 - 1121
Copyright
Copyright © Cambridge University Press 2007

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