Analysis of the redox status and its effect on the proliferation of Plasmodium falciparum in genetically different erythrocytes

Abstract

Malaria is one of the most dangerous tropical diseases of our time with more than one million deaths per annum. The worst form of malaria, the malaria tropica, is caused by the parasite Plasmodium falciparum. However some genetic mutations of haemoglobin like sickle cell haemoglobin (HbS) or enzymopathies like glucose-6-phosphate dehydrogenase deficiency are leading to a protection against severe falciparum malaria. Despite years of research the precise mechanisms of protection still has to be discovered although there are few hypothesis. Besides the suggestion of a better innate immune response through an increased degree of phagocytosis, a main role could also be the pro-oxidative habitat inside the red blood cells (RBC) which attenuate the parasite proliferation. Oxidative stress plays a major role for example during the sickle cell disease. By investigation of the redox metabolism of P. falciparum while culturing transgenically modified parasites in abnormal erythrocytes, we will validate the protective role of genetically different red blood cells by focussing on the oxidant defence systems in falciparum malaria and analyse the inhibitory profile of the plasmodial glyoxalase I and II in vitro and in vivo. This should lead us to the identification of novel drug approaches for targeting this deadly pathogen. (AU)