PhD Oral Defense: Haemonchus contortus ABC Transporters Linked to Macrocyclic Lactone Resistance
PhD Oral Defense of Pablo Godoy Rosas, Institute of Parasitology.
Haemonchus contortus is a parasitic nematode distributed all around the world where ruminants graze and decreases animal production. In order to control this veterinary helminth, anthelmintic drugs are still the main strategy in veterinary medicine. One particular anthelmintic class is the macrocyclic lactones (MLs), which has remarkable efficacy against endo and ectoparasites in animal and human health. Unfortunately, due to the continuous use of the MLs against parasitic nematodes, including H. contortus, has led to drug resistance, that limits their use. In H. contortus, one of the resistance mechanisms involved could be the over expression of P-glycoproteins (PGPs) and possibly other nematode transporters, which belong to the ATP-Binding-Cassette (ABC) transporter protein family. The activity of the ABC transporters is the extrusion of many unrelated compounds across the cell membrane. In the host, these plasma membrane proteins are expressed in different organs and tissues influencing the bioavailability and pharmacokinetics of different substrates including the MLs. In H. contortus and other nematodes, some ABC transporters have shown a consistent link with ML resistance. In addition, studies characterizing the interaction between mammalian ABC transporters with ML such as avermectins, have established a strong interaction between these compounds and PGP activity, transporting these drugs and contributing to their elimination.
The goal of this project was the characterization of some H. contortus P-glycoproteins (Hco-PGP-2, Hco-PGP-9.1 and Hco-PGP-16) and their interaction with MLs such as avermectins and moxidectin in order to elucidate if these transporters may play a role in ML resistance in this parasite.