Plasmodium falciparum: characterization of organelle migration during merozoite morphogenesis in asexual malaria infections.

Treatment of asexual Plasmodium falciparum infections with the microtubule stabilizing agents Taxol or epothilone A prevents the depolymerization of nuclear microtubules. Serial thin sectioning of treated parasites revealed the presence of polymerized nuclear microtubule assemblies extending from spindle pole bodies into the forming merozoites in late stage infections. This organization prevented daughter merozoites from pinching off the mother schizont during merogony. An electron-dense collar was apparent at the junction of the budding parasites and the schizont plasma membrane, suggesting the presence of a contractile, actin-myosin ring. Examination of Taxol or EpA arrested parasites provided new information about the merogonic process and the control of organelle migration. Drug treatment did not affect the migration or polarity of the rhoptries and micronemes. Ultrastructural characterization of drug-treated trophozoites identified an assembly of smooth vesicles and short tubules adjacent to the parasite nuclei. During merogony, these membranes were observed as flattened cisternae with dilated rims that appeared to be coated. The morphology and location of these membranes suggest that they may be the parasite Golgi apparatus. This investigation reveals that the antimalarial activity of microtubule stabilizing agents is due to their inhibition of merozoite formation.