Summa.ryWhen merozoites of the malaria parasite Plasmodiumfaki~rum are released from infected erythrocytes and invade new red cells, a component of a protein complex derived from the merozoite surface protein 1 (MSP-1) precursor undergoes a single proteolytic cleavage known as secondary processing. This releases the complex from the parasite surface, except for a small membrane-bound fragment consisting of two epidermal growth factor (EGF)-like domains, which is the only part of MSP-1 to be carried into invaded erythrocytes. We report that, of a group of monoclonal antibodies specific for epitopes within the EGF-like domains, some interfere with secondary processing whereas others do not. Those that most effectively inhibit processing have previously been shown to prevent invasion. Other antibodies, some of which can block this inhibition, not only do not prevent invasion but are carried into the host cell bound to the merozoite surface. These observations unequivocally demonstrate that the binding of antibody to the COOH-terminal region of MSP-1 on the merozoite surface may not be su~cient to prevent erythrocyte invasion, and show that the interaction of different antibodies with adjacent epitopes within the EGF-like domains of MSP-1 can have distinct biochemical effects on the molecule. Inhibition of MSP-1 processing on merozoites may be a mechanism by which protective antibodies interrupt the asexual cycle of the malaria parasite.
The antimalarial activity of rifampicin, a specific inhibitor of bacterial ribonucleic acid (RNA) polymerase, was confirmed with Plasmodium falciparum in vitro and with P. chabaudi in vivo. The viability of ring forms of P. falciparum, measured by [3H]hypoxanthine and [14C]isoleucine uptake, was significantly reduced within 5 h of exposure to 2.5 microM rifampicin, the 50% inhibitory concentration. Streptolydigin and tagetitoxin, other specific inhibitors of bacterial RNA polymerase, were much less effective as antimalarials. A rifampicin-tolerant sub-line of P. falciparum was selected in vitro. When released from drug pressure, the tolerant line showed appreciably greater rates of incorporation of precursors and growth than the parent line, but over a period of months these characteristics gradually reverted. Rifampicin was effective against a chloroquine-resistant line of P. falciparum and the rifampicin-tolerant line had increased chloroquine sensitivity. Treatment of patent parasitaemias of P. chabaudi in mice with more than 100 mg/kg rifampicin twice daily significantly reduced the parasitaemia within 24 h and parasites were barely detectable on blood films by the fourth day. Recrudescence occurred on release of drug pressure.
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