STAUROSPORINE INHIBITS INVASION OF ERYTHROCYTES BY MALARIAL MEROZOITES

Staurosporine, a protein kinase inhibitor, inhibits the invasion of rh esus monkey erythrocytes by Plasmodium knowlesi merozoites with an IC5 0 of 250 nM. The drug exerts its effects primarily on the merozoite, w ith little or no effect on the erythrocyte. Okadaic acid, an inhibitor of protein phosphatases, can partially abrogate the inhibitory effect s of staurosporine. Staurosporine arrests invasion at a step which is ultrastructurally similar to the arrest caused by cytochalasins B and D: the merozoite attaches, apically reorients, and forms a junction wi th the erythrocyte, but it does not internalize. These results suggest that protein phosphorylation within the merozoite plays an important role in the internalization Step of invasion. (C) 1994 Academic Press, Inc.