ANALYSES OF MECHANISMS FOR PLASMODIUM ADAPTATION TO THE HOST ERYTHROCYTES

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To obtain fundamental knowledge necessary for developing malaria vaccines and new antimalarials, mechanisms for adaptation by malaria parasites to their host erythrocytes have been studied at the molecular and cellular levels. Results are as follows:I. Membrane transport of metabolites in malaria-infected cells. (1) Plasmodium falciparum grows well in human erythrocytes, whose potassium levels ae reduced greatly by treatment with ouabain. (2) An appearance of small pores in the membranes of P. yoelii-infected cells lead to increase in the uptake of 2-deoxy-D-glucose. An electrical potential of protons across the plasma membrane of intraerythrocytic parasites is coupled to an uphill active uptake of 2-deoxy-D-glucose. (3) The mitochondrion of P. yoelii has an inside negative membrane potential.II. Polymorphism of a surface antigen of P. falciparum merozoite. (1) The gene for a precursor (p190) to major merozoite surface antigens of P. falciparum has been cloned and sequenced. Comparisons of the p190 gene from several parasite isolates has revealed both conserved and variable regions. (2) Variations in the sequence are not widely polymorphic but fall into two types. Southern blot analyses of genomic DNA from 14 isolates has shown that the p190 gene is dimorphic alles. it is suggested that intragenic recombination of the p190 alles creates the antigen's polymorphism.III. Calcium metabolism of malaria-infected erythrocytes. (1) Disturbance of calcium metabolism of P. yoelii- and P. falciparum-infected cells by Ca^<2+> ionophore, calcium antagonists and calmodulin inhibitors results in the death of the parasites.