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Supervisor:

Prof. Dr. Georg von Samson-Himmelstjerna

Lab Address:

Freie Universität Berlin, Institute for Parasitology and Tropical Veterinary Medicine, Centre for Infection Medicine, Robert von Ostertag-Str. 7, D-14163 Berlin

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Project description:

Following decades of heavy reliance of anthelmintics concerning the treatment and control of helminth infections in both human and veterinary medicine, nowadays, more and more drug resistant worm populations occur. This meanwhile represents one of the most urgent threats to animal health and productivity. Furthermore, this also is a great concern for the success of mass-drug-administration programs e.g. in school children in many countries where this is employed particularly to control the highly endemic Ascaris spp. infections. Based on recent own findings ascarids, when compared to other intestinal helminths such as strongyles, obviously exhibit a different mechanism of resistance against the benzimidazole anthelmintics. These are the most frequently used drugs to treat this group of worms both in humans and animals. While in strongyles benzimidazole resistance is mostly associated with amino-acid changes in a beta-tubulin protein as the drug target, this mechanism is lacking in resistant ascarid populations. This lack of understanding of the BZ resistance mechanism is a serious constraint for any attempts to monitor drug efficacy in the field.

Accordingly, this project aims at elucidating this issue by experimentally examining the role of ascarid drug efflux and metabolizing pathways (DEMP). These include P-glycoprotein (Pgp) transmembrane transporters, cytochrome P 450 enzymes or UGT-transferases. Ascaris DEMPs will be expressed and functionally characterized in the C. elegans model. In addition, gene expression pre/post benzimidazole treatment will be evaluated in Ascaris field isolates as well as following in vitro exposure of live worms and Ascaris eggs. This will show if DEMP related mechanisms provide resistance to the standard drug class employed for the treatment of human/livestock Ascaris infections.