Growth inhibition of Plasmodium falciparum in in vitro cultures by selective action of tryptophan-N-formylated gramicidin incorporated in lipid vesicles.

G N Moll, V van den Eertwegh, H Tournois, B Roelofsen, J A Op den Kamp, L L van Deenen

Centre for Biomembranes and Lipid Enzymology, University of Utrecht, The Netherlands.

Biochimica et biophysica acta 1991 Feb 25

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We studied the differential effect of tryptophan-N-formylated gramicidin on uninfected and Plasmodium falciparum-infected erythrocytes. Trp-N-formylated gramicidin induces a much faster leakage of K+ from infected cells than from uninfected cell whereas, and at an even lower concentration, gramicidin A' causes a rapid K+ leakage from both uninfected and infected cells. We also studied the effect of Trp-N-formylated gramicidin and gramicidin A' incorporated in liposomes on the growth of Plasmodium falciparum in an in vitro culture. Incorporation of Trp-N-formylated gramicidin in the membranes of so-called 'stealth' vesicles strongly decreases the concentration needed to induce 50% inhibition of parasite growth. Moreover, no decrease in the K+ content of uninfected cells was observed when cells were exposed to liposome-incorporated Trp-N-formylated gramicidin at a concentration which causes full inhibition of parasite growth. These observations strongly suggest that Trp-N-formylated gramicidin incorporated in 'stealth' vesicles ends up specifically in the infected cell, thereby inhibiting the growth of the growth of the malaria parasite.

Citation

G N Moll, V van den Eertwegh, H Tournois, B Roelofsen, J A Op den Kamp, L L van Deenen. Growth inhibition of Plasmodium falciparum in in vitro cultures by selective action of tryptophan-N-formylated gramicidin incorporated in lipid vesicles. Biochimica et biophysica acta. 1991 Feb 25;1062(2):206-10