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

作者：Wilkinson Richard; Law Christopher J; Hoey Elizabeth M; Fairweather Ian; Brennan Gerard P; Trudgett Alan^*

来源：Molecular and Biochemical Parasitology, 2012, 186(1): 69-72.

DOI：10.1016/j.molbiopara.2012.08.008

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

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 %26quot;resistant%26quot; 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.

• 出版日期2012-11