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Plasmodium falciparum : Differential Sensitivity In Vitro to E‐64 (Cysteine Protease Inhibitor) and Pepstatin A (Aspartyl Protease Inhibitor)
Author(s) -
BAILLY ERIC,
JAMBOU RONAN,
SAVEL JEAN,
JAUREGUIBERRY GINETTE
Publication year - 1992
Publication title -
the journal of protozoology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.067
H-Index - 77
eISSN - 1550-7408
pISSN - 0022-3921
DOI - 10.1111/j.1550-7408.1992.tb04856.x
Subject(s) - pepstatin , plasmodium falciparum , cysteine protease , protease inhibitor (pharmacology) , in vitro , protease , chemistry , biochemistry , enzyme , biology , virology , malaria , human immunodeficiency virus (hiv) , immunology , viral load , antiretroviral therapy
We investigated the effect of a cysteine proteinase inhibitor (E‐64) and an aspartyl proteinase inhibitor (Pepstatin A) on asexual erythrocytic stages of Plasmodium falciparum in culture. These two protease inhibitors showed different patterns of activity. E‐64 acted preferentially against trophozoite and schizont stages. After 48 h incubation at high concentrations of E‐64 (28, 140, 280 μM), growth was totally abolished and the parasites presented characteristic enlarged food vacuoles. Morphological alterations were also seen after shorter incubation periods (6 h at 28 μM) or 12 h at the inhibitory concentration 50% (12 μM), but an additional culture period (24 h) in inhibitor‐free medium allowed normal parasite development, demonstrating a parasitostatic effect. E‐64 acts on parasite multiplication; the normal merozoite maturation was altered and the normal reinvasion process partially impaired. Pepstatin A used at the inhibitory concentration 50% (4 μM) killed the parasites before trophozoite development and had a major effect on schizonts maturation. No altered parasite development occurred during an additional culture period without Pepstatin A, demonstrating a parasiticidal effect. E‐64 and Pepstatin A used in combination inhibit the parasite growth with a strong synergistic effect.