Haemonchus contortus: sequence heterogeneity of internucleotide binding domains from P-Glycoproteins and an association with avermectin/milbemycin resistance

P-Glycoproteins are transmembrane proteins associated with acquired multidrug resistance in mammalian cells and some protozoan parasites by a process of active drug export. P-glycoproteins contain two nucleotide binding domains which couple ATP to the drug transport process. The region between the n...

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Bibliographic Details
Published in:Experimental parasitology 1999-03, Vol.91 (3), p.250-257
Main Authors: Sangster, N.C, Bannan, S.C, Weiss, A.S, Nulf, S.C, Klein, R.D, Geary, T.G
Format: Article
Language:English
Subjects:
animal parasitic nematodes
binding
drug resistance
glycoproteins
Haemonchus contortus
resistance mechanisms
sheep
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Summary:P-Glycoproteins are transmembrane proteins associated with acquired multidrug resistance in mammalian cells and some protozoan parasites by a process of active drug export. P-glycoproteins contain two nucleotide binding domains which couple ATP to the drug transport process. The region between the nucleotide binding domains of P-glycoproteins, termed the internucleotide binding domain (IBD), was PCR-amplified from adult and larval cDNA libraries using degenerate primers. The 11 clones isolated by this method fall into several distinct groups, with one group of alleles displaying between 82 and 99% identity at the nucleotide level. This sets a baseline for sequence variation of transcribed alleles from a parasitic nematode. Northern blotting showed that P-glycoprotein genes are transcribed in a developmentally regulated fashion in Haemonchus contortus. Southern blots of H. contortus drug-resistant isolates with an IBD probe revealed a pattern consistent with the involvement of P-glycoprotein in resistance to avermectin/milbemycin anthelmintics.
ISSN:0014-4894
1090-2449
DOI:10.1006/expr.1998.4373