Ornithine decarboxylase inhibition and the malaria-infected red cell: a model for polyamine metabolism and growth

Abstract

The addition of DL-alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, to human Plasmodium falciparum-infected red cells in continuous culture decreased both parasite growth and intracellular polyamine concentrations. Growth of P. falciparum in infected red cells was assessed by parasite counts and by assays for macromolecular syntheses of protein, DNA and RNA. Polyamine concentrations were measured by an automated high-performance liquid chromatography method. Concentrations of DL-alpha-difluoromethylornithine greater than 0.3 mM decreased intracellular levels of putrescine and spermidine, reduced ornithine decarboxylase activity and inhibited growth and maturation of the intracellular parasite at the trophozoite stage. There was a concomitant decrease in the synthesis of protein and nucleic acids in the infected cells. The use of this parasitized red cell model system together with polyamine inhibitors provide means of studying polyamine synthesis and cell growth in the design of new antimalarial therapy.