The Putative Cyclooctadepsipeptide Receptor Depsiphilin of the Canine Hookworm Ancylostoma caninum

Abstract

The G-Protein-coupled receptor Hc110-R of Haemonchus contortus and its orthologue in Caenorhabditis elegans, the latrophilin-like protein 1 (LAT-1), were shown to play a role in the mode of action of the new anthelmintic compound emodepside. C. elegans LAT-1 knockout mutants showed a decreased paralysing effect of emodepside on the pharyngeal muscle. In the present study, the LAT-1 orthologue in the canine hookworm Ancylostoma caninum was identified and named depsiphilin. To obtain more information about the regulation of this receptor and to facilitate phylogenetic and evolutionary analyses of parasitic nematode genes, the genomic structure of A. caninum depsiphilin was investigated. High consistency regarding the position of introns in comparison to C. elegans LAT-1 was observed, providing indication of the same origin of the genes. With a view to possible differences in efficacy of emodepside on different developmental stages, we analysed the transcript level of A. caninum depsiphilin in eggs, L1, L3, male and female adult worms using quantitative real-time PCR. Depsiphilin is transcribed in all five examined stages, but we found a significantly lower transcript level in third-stage larvae. A correlation between these findings and a reduced emodepside activity remains to be investigated.