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 erythrocyte. Many proteins are secreted from the parasite and are subsequently found at specific locations within the host cell. To elucidate the importance of protein secretion for parasite survival, infected red blood cells (IRBC) were subjected to the fungal metabolite brefeldin A (BFA) and to incubation at 15 degrees C, treatments that inhibit protein secretion and parasite development. Evidence is provided that retardation 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 ring stages loose 50% of their competence to develop to trophozoites after 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 viability of trophozoites cultured at 15 degrees C or in the presence of BFA is completely abolished within 24 h.
Benting
J
J
Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Ansorge
I
I
Paprotka
K
K
Lingelbach
K R
KR
D000818:Animals; D020126:Brefeldin A; D003517:Cyclopentanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D015800:Protozoan Proteins / Q000378:metabolism*; D013696:Temperature
D003517:Cyclopentanes; D011500:Protein Synthesis Inhibitors; D015800:Protozoan Proteins; D020126:Brefeldin A