Authors

C RiversC Lilley¹; V O'ConnerP UrwinU Ebbinghaus-KintscherL Holden-Dye ¹ School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds. LS2 9JT, UK.

Discussion

The cyclo-octadepsipeptide anthelmintic emodepside targets the calcium and voltage-activated K+ channel SLO-1 channel (Guest et al. 2007) in the free-living nematode Caenorhabditis elegans and inhibits neuromuscular function. Whilst the effect of emodepside on C. elegans and a range of animal parasitic nematodes has been well characterised (Welz et al. 2011) its action on plant parasitic nematodes has yet to be described. This study provided a comparative analysis of the effect of emodepside effect on and C. elegans and the potato cyst nematode Globodera pallida.
The effect of emodepside on C. elegans feeding, reproduction, motility and viability was directly compared to its effect on G. pallida stylet thrusting, egg hatching, motility and viability. Interestingly emodepside was found to have biological activity in all of the assays conducted for G. pallida with a comparable efficacy to C. elegans. It potently inhibited G. pallida motility, EC50 679 nM and stylet thrusting, EC50 802 nM. Hatching assays with G. pallida showed that emodepside affects hatching at higher doses (≥5µM). A high affinity SLO-1 antagonist verruculogen blocked the inhibitory effect of emodepside on G. pallida motility. Furthermore, a bioinformatic search has identified an orthologue of C. elegans slo-1 in the G. pallida genome sequence. These data suggest emodepside impacts on G. pallida behaviours through a SLO-1 dependent mechanism.
Currently we are cloning and expressing G. pallida slo-1 to permit functional and pharmacological characterisation.
Acknowledgements: Caroline Rivers is funded by a BBSRC CASE studentship with Bayer CropScience.
Guest M, Bull K, Walker RJ, Amliwala K, O'Connor V, Harder A, Holden-Dye L, Hopper NA (2007) The calcium-activated potassium channel, SLO-1, is required for the action of the novel cyclo-octadepsipeptide anthelmintic, emodepside, in Caenorhabditis elegans. Int J Parasitol 37: 1577-1588 Welz C, Krüger N, Schniederjans M, Miltsch SM, Krücken J, Guest M, Holden-Dye LM, Harder A, von Samson-Himmelstjerna G (2011) SLO-1-channels of parasitic nematodes reconstitute locomotor behaviour and emodepside sensitivity in Caenorhabditis elegans slo-1 loss of function mutants. PLoS Pathog 7: e1001330