PhD Oral Defense: the effect of antimalarial drugs on intracellular pH in Plasmodium falciparum
PhD Defense of Juliane Wunderlich, Institute of Parasitology
Malaria is one of the most severe public health problems worldwide and a leading cause of death and disease in developing countries. The alarming spread of resistance to first-line as well as second- and third-line antimalarials accentuates the need for the better biochemical and physiological understanding of the interaction of malaria parasites with these drugs to develop novel therapeutic strategies that either inhibit or circumvent resistance mechanisms.
The digestive vacuole (DV) of Plasmodium falciparum is the site of action of many antimalarials and plays a pivotal role in drug resistance. Its membrane is thought to contain pumps and transporters that are implicated in the maintenance of the acidic pH in the DV lumen (pHDV) and the transport of antimalarials. The low pHDV is important for the functions of this compartment, including hemoglobin degradation and heme detoxification. A possible alteration of pHDV in response to quinoline-containing antimalarials (QCAs) has remained controversial due to the lack of accurate measurements and the mechanisms of action of these drugs are still unclear.