CHEMICAL AND THERMAL INHIBITION OF PROTEIN SECRETION HAVE STAGE-SPECIFIC EFFECTS ON THE INTRAERYTHROCYTIC DEVELOPMENT OF PLASMODIUM-FALCIPARUM IN-VITRO

The intraerythrocytic stages of the human malaria parasite Plasmodium falciparum induce a variety of physiological changes of the host eryth rocyte. Many proteins are secreted from the parasite and are subsequen tly found at specific locations within the host cell. To elucidate the importance of protein secretion for parasite survival, infected red b lood cells (IRBC) were subjected to the fungal metabolite brefeldin A (BFA) and to incubation at 15 degrees C, treatments that inhibit prote in secretion and parasite development. Evidence is provided that retar dation of parasite development in the presence of BFA correlates with an inhibition of protein secretion. Incubation at 15 degrees C and BFA reversibly arrest parasite development at the ring stage. Arrested ri ng stages loose 50% of their competence to develop to trophozoites aft er 1.5 days of treatment with BFA and after approximately 4 days at 15 degrees C. BFA affects development of trophozoites at concentrations similar to those required to arrest rings. In contrast to rings, the v iability of trophozoites cultured at 15 degrees C or in the presence o f BFA is completely abolished within 24h.