An amino acid substitution in Fasciola hepatica P-glycoprotein from triclabendazole-resistant and triclabendazole-susceptible populations

R. Wilkinson, C.J. Law, E.M. Hoey, I. Fairweather, G.P. Brennan, A. Trudgett

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24 Citations (Scopus)
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Abstract

Control of fasciolosis is threatened by the development of anthelmintic resistance. Enhanced triclabendazole (TCBZ) efflux by ABC transporters such as P-glycoprotein (Pgp) has been implicated in this process. A putative full length cDNA coding for a Pgp expressed in adult Fasciola hepatica has been constructed and used to design a primer set capable of amplifying a region encoding part of the second nucleotide binding domain of Pgp when genomic DNA was used as a template. Application of this primer set to genomic DNA from TCBZ-resistant and -susceptible field populations has shown a significant difference in the alleles present. Analysis of an allele occurring at a three-fold higher frequency in the "resistant" population revealed that it was characterised by a serine to arginine substitution at residue 1144. Homology modelling studies have been used to locate this site in the Pgp structure and hence assess its potential to modify functional activity. © 2012 Elsevier B.V.
Original languageEnglish
Pages (from-to)69-72
Number of pages4
JournalMolecular and Biochemical Parasitology
Volume186
Issue number1
Early online date11 Sep 2012
DOIs
Publication statusPublished - 01 Nov 2012

Keywords

  • Fasciola hepatica; Anthelmintic resistance; P-glycoprotein; SNP

ASJC Scopus subject areas

  • Parasitology
  • Molecular Biology

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