Transgenically expressed Parascaris P-glycoprotein-11 can modulate ivermectin susceptibility in Caenorhabditis elegans. Issue 2 (August 2015)

• Record Type: Journal Article
• Authors: Janssen, I. Jana I.; Krücken, Jürgen; Demeler, Janina; von Samson-Himmelstjerna, Georg
• Is Part Of: International journal for parasitology. Volume 5:Issue 2(2015)
• Page Start: 44
• Page End: 47
• Publication Date: 2015-08
• Subjects: Caenorhabditis elegans -- Macrocyclic lactone -- Resistance -- Thrashing assay -- Equine parasites; Parasitic diseases -- Chemotherapy -- Periodicals; Drug resistance -- Periodicals; 616.96061
• DOI: 10.1016/j.ijpddr.2015.03.003
• Languages: English
• ISSNs: 2211-3207

Abstract

Highlights: Parascaris sp. pgp-11 expressed in Caenorhabditis elegans . Thrashing assay reveals increased EC50 for ivermectin in Pgp-11 transgenic worms. C. elegans suitable as model for functional analysis of ascarid-Pgps. Abstract: P-glycoproteins (Pgps) are suspected to mediate drug extrusion in nematodes contributing to macrocyclic lactone resistance. This association was recently shown for Parascaris Pgp-11 . Ivermectin resistance was correlated with the presence of three pgp-11 single nucleotide polymorphisms and/or increased pgp-11 mRNA levels. In the present study, the ability of Pgp-11 to modulate ivermectin susceptibility was investigated by its expression in a pgp-11 -deficient Caenorhabditis elegans strain. Expression of Parascaris pgp-11 in two transgenic lines significantly decreased ivermectin susceptibility in a motility (thrashing) assay conducted in liquid medium. The EC50 values increased by 3.2- and 4.6-fold in the two lines relative to a transgenic control strain. This is the first report on the successful functional analysis of a parasitic nematode Pgp in the model organism C. elegans .