The Use of Forward Genetic Approaches to Investigate the Mechanism of Anthelmintic Resistance in H. contortus (Anthelmintics: From discovery to resistance II San Diego USA)

  • Umer Naveed Chaudhry (Speaker)

Activity: Academic talk or presentation typesOral presentation


Control of parasitic nematodes are heavily dependent upon the use of anthelmintics. Resistance to the all major class of anthelmintics has been observed in livestock. Most parasitic nematodes are difficult experimental subjects for making mechanistic study of anthelmintic resistance (AR). The small ruminant parasite H. contortus is a more amenable model system in which to study mechanism and genetics of AR based on the number of aspects of parasite biology. Genetic crossing of parasitic nematodes is a difficult task because the adult parasites are concealed in the host. Nevertheless, the high fecundity of H. contortus and ability to viably transplant into the abomasum makes genetic crossing feasible. Our approach involves genetic mapping of AR loci in the progeny of a F2 mapping crosses generated between two well characterized genetically divergent isolates of H. contortus, the anthelmintic sensitive genome isolate-MHco3 (ISE) and multi-drug resistant isolate-MHco18 (UGA). In this particular study, L4 female worms from a drug susceptible strain were transplanted with L4 male worms from a drug resistant strain directly into the abomasum of a recipient ovine host. Eggs recovered in the faeces of the recipient host (F1 progeny) were cultured to the L3 stage in vitro and then used to orally infect another host to obtain F1 adult worms. These F1 adult worms were surgically recovered from the abomasum on necropsy and used in the next generation F2 progeny. The sensitivity of the F1 and F2 progeny to AR was assessed using in-vitro bioassays with free living life stages. A panel of microsatellite markers was also used to monitor the back crossing procedure of F1 and F2 progeny. We demonstrate that after few arounds of backcrossing, worms that are phenotypically resistant to AR has similar genetic background to the susceptible reference strain. This work provides a novel genetic approach to study anthelmintic resistance and provides a proof a concept of the use of potentially extremely powerful forward genetic in an important model parasite. The strains generated from this study will be the valuable resources to further look for the evidence of genetic linkage to AR resistance conferring locus providing a starting point for more detailed studies of the genome wide region to identify AR mutations.
Event titleAnthelmintic Resistance II USA
Event typeConference