Requirement of malarial protease in the invasion of human red cells by merozoites of Plasmodium falciparum.

Abstract

Highly synchronous cultures of the erythrocyte stages of Plasmodium falciparum were used to determine the effects of a number of protease inhibitors on parasite development and merozoite invasion. Leupeptin, N-tosyl-L-lysyl chloromethylketone and pepstatin at a concentration greater than 0.05 mM were deleterious to both parasite development and merozoite invasion whereas aprotinin, antipain, alpha-1-antitrypsin and soybean trypsin inhibitor had no effect at a concentration of 0.5 mM. On the other hand, N-tosyl-L-phenylalanyl chloromethylketone and phenylmethylsulfonylfluoride at a concentration of 1 mM and chymostatin at a concentration of 0.15 mM inhibited merozoite invasion but were not deleterious to parasite development. Pretreatment of red cells with these three inhibitors did not block merozoite invasion. These results suggested that a chymotrypsin-like activity of the merozoite is important in the invasion process.