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ABC transporters and β-tubulin in macrocyclic lactone resistance: prospects for marker development

Published online by Cambridge University Press:  03 July 2007

R. K. PRICHARD  and
A. ROULET
R. K. PRICHARD*
Affiliation:
Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste-Anne-de-Bellevue, Quebec, Canada, H9X 3V9
A. ROULET
Affiliation:
Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste-Anne-de-Bellevue, Quebec, Canada, H9X 3V9
*
*Corresponding author: Institute of Parasitology, McGill University, 21111 Lakeshore road, Ste-Anne-de-Bellevue, Quebec, Canada, H9X 3V9. Tel: +1-514-398-7729. Fax: +1-514-398-7857. E-mail: [email protected]
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Summary

Macrocyclic lactones (MLs) are highly lipophilic anthelmintics which are known to bind to and open ligand-gated ion channels. However, these anthelmintics, and particularly the avermectin members of the ML class of endectocides, are potent substrates for ABC transporters and these transporters may regulate drug concentration in both the host and the parasite. There is accumulating evidence that ivermectin (IVM), and to a lesser extent moxidectin (MOX), selects for certain alleles of P-glycoprotein and other ABC transporter genes, selects for constitutive overexpression of some of these gene products, and induces overexpression of some P-glycoproteins in nematodes. However, such mechanisms of ML resistance do not easily lend themselves to the identification of SNP markers for resistance because of the diversity of ABC transporters in nematodes, the apparent diversity of effects of different MLs, and because regulatory elements for ABC transporter gene expression are not well understood in nematodes. Another non ligand-gated ion channel gene which appears to be under IVM selection, at least in Onchocerca volvulus and Haemonchus contortus, is β-tubulin, and a simple genetic test for this selection has been described in O. volvulus. However, further work is required to elucidate a reliable marker associated with this gene in H. contortus or other parasitic nematodes of livestock. The possible involvement of ABC transporter genes and β-tubulin in ML resistance provides a start in developing our understanding of this phenotype and markers for its detection in field populations of parasitic nematodes. However, more work is required before these leads can provide practical SNP markers for ML resistance.

Keywords

Macrocyclic lactone anthelminticsivermectinmoxidectindrug resistancenematodeABC transportersP-glycoproteinsβ-tubulin
Type
Research Article
Information
Parasitology , Volume 134 , Special Issue 8: MARKERS FOR ANTHELMINTIC RESISTANCE , August 2007 , pp. 1123 - 1132
Copyright
Copyright © Cambridge University Press 2007

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