MODULATION OF THE GROWTH OF PLASMODIUM-FALCIPARUM IN-VITRO BY PROTEINSERINE THREONINE PHOSPHATASE INHIBITORS/

To elucidate the physiological roles of the protein serine/threonine p hosphatases of P. falciparum, first we identified and characterized ph osphatase activities of Plasmodium falciparum enzymologically and phar macologically. We have demonstrated that P. falciparum possesses phosp hatase-l-like activities predominantly over phosphatase-2A-like activi ties, while erythrocytes possess mainly phosphatase-2A-like activities . Theta, we examined the effects of okadaic acid and calyculin A, pote nt inhibitors of protein phosphatase 1 and 2A, on the growth of P. fal ciparum in vitro. Both of the drugs inhibited parasite growth dose dep endently. The manner of growth inhibition by calyculin A and okadaic a cid suggested that these drugs inhibit parasite growth mainly by inhib iting parasite phosphatase-l-like activities. Both drugs were shown to inhibit the growth of three different developmental stages of parasit es-ring forms, trophozoites, and schizonts-and inhibit trophozoites th e most. This is the first report on P. falciparum protein serine/threo nine phosphatase activities, which are essential to regulate the eryth rocytic stage of parasite growth. (C) 1998 Academic Press.