Investigation of the mode of action of, and the resistance mechanisms against, nitro drugs in Giardia lamblia
Giardia lamblia is a protozoan parasite that may cause severe diarrhea in humans and various animal species. Chemotherapeutical treatment of the disease is mostly based on the use of the nitro drug metronidazole but unfortunately increasing rates of resistance against this drug have been noted. Our project is focused on the investigation of enzymes that are involved in the mode of action of, and resistance formation against, metronidazole and other nitro drugs.
Giardia contains several nitroreductases that have been adopted from bacteria via lateral gene transfer. Currently, we investigate the metabolic functions of these enzymes (or the enzymatic complexes containing nitroreductases, respectively) particularly considering the question if they are able to (i) activate nitro drugs thus contributing to the mode of action of these drugs or (ii) detoxify nitro drugs thus contributing to giardial resistance formation.
Furthermore, we examine if adoption of these bacterial nitroreductases provides an evolutionary advantage to the parasite in that these enzymes facilitate giardial survival within the hostile intestinal environment. In general, we expect that our project will indicate novel chemotherapeutical avenues to efficaciously treat (nitro drug-resistant) giardiasis in humans as well as in different in animal hosts.