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Vet Parasitol. 2008 Mar 25;152(1-2):101-7. doi: 10.1016/j.vetpar.2007.12.001. Epub 2007 Dec 8.

P-glycoprotein selection in strains of Haemonchus contortus resistant to benzimidazoles.

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  • 1Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste.-Anne-de-Bellevue, QC H9X 3V4, Canada. wblack@tiho-hannover.de

Abstract

Anthelmintic resistance in parasitic nematodes of livestock is a chronic problem in many parts of the world. Benzimidazoles are effective, broad-spectrum anthelmintics that bind to and selectively depolymerise microtubules. Resistance to the benzimidazoles, however, developed quickly and is caused by genetic changes in genes encoding beta-tubulins, subunits of microtubules. In Haemonchus contortus, resistance to avermectins has been correlated with genetic changes at a gene encoding a P-glycoprotein, a cell membrane transport protein that has a very high affinity for ivermectin. The substrate specificity of P-glycoprotein is very broad, and resistance to benzimidazoles can be modulated by lectins specific for P-glycoprotein. We investigated the possibility that genetic changes in P-glycoprotein might be correlated with benzimidazole resistance in nematodes. An analysis of restriction fragment length polymorphisms of a P-glycoprotein gene from a sensitive and a cambendazole-selected strain of H. contortus, derived from the sensitive strain, showed a significant difference in allele frequencies between strains. The frequency of one allele in particular increased substantially. The same allele was also found at a high frequency in an independently derived thiabendazole-selected field isolate. We present genetic evidence of selection at a P-glycoprotein locus during selection for benzimidzole resistance in H. contortus.

PMID:
18241994
[PubMed - indexed for MEDLINE]
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