Growth inhibition of Plasmodium falciparum in in vitro cultures by selective action of tryptophan-N-formylated gramicidin incorporated in lipid vesicles.
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.
Moll
G N
GN
Centre for Biomembranes and Lipid Enzymology, University of Utrecht, The Netherlands.
van den Eertwegh
V
V
Tournois
H
H
Roelofsen
B
B
Op den Kamp
J A
JA
van Deenen
L L
LL
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D004337:Drug Carriers; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D006096:Gramicidin / Q000008:administration & dosage / Q000494:pharmacology* / Q000031:analogs & derivatives; D066298:In Vitro Techniques; D008081:Liposomes; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D011188:Potassium / Q000097:blood
D004337:Drug Carriers; D008081:Liposomes; C067987:tryptophan-N-formylgramicidin; D006096:Gramicidin; D011188:Potassium