P-glycoproteins play a role in ivermectin resistance in cyathostomins

Publication date: December 2017 Source:International Journal for Parasitology: Drugs and Drug Resistance, Volume 7, Issue 3 Author(s): L.E. Peachey, G.L. Pinchbeck, J.B. Matthews, F.A. Burden, A. Lespine, G. von Samson-Himmelstjerna, J. Krücken, J.E. Hodgkinson Anthelmintic resistance is a global problem that threatens sustainable control of the equine gastrointestinal cyathostomins (Phylum Nematoda; Superfamily Strongyloidea). Of the three novel anthelmintic classes that have reached the veterinary market in the last decade, none are currently licenced in horses, hence current control regimens focus on prolonging the useful lifespan of licenced anthelmintics. This approach would be facilitated by knowledge of the resistance mechanisms to the most widely used anthelmintics, the macrocyclic lactones (ML). There are no data regarding resistance mechanisms to MLs in cyathostomins, although in other parasitic nematodes, the ABC transporters, P-glycoproteins (P-gps), have been implicated in playing an important role. Here, we tested the hypothesis that P-gps are, at least in part, responsible for reduced sensitivity to the ML ivermectin (IVM) in cyathostomins; first, by measuring transcript levels of pgp-9 in IVM resistant versus IVM sensitive third stage larvae (L3) pre-and post-IVM exposure in vitro. We then tested the effect of a range of P-gp inhibitors on the effect of IVM against the same populations of L3 using the in vitro larval development test (LDT) and larva...
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research