Plasmodium Proliferation in Human Erythrocytes: How, Why, and Who?

Malaria is a life-threatening disease that is caused by unicellular eukaryotic parasites of the genus Plasmodium, with P. falciparum being responsible for the most severe form of human malaria. In the clinically relevant blood stage of infection, the parasite proliferates inside erythrocytes via an unusual cell cycle called schizogony. A hallmark of schizogony is the presence of multinucleated cells where the nuclei divide asynchronously despite residing in a common cytoplasm. To investigate the mechanistic basis of schizogony and its molecular determinants, we combine long-term live-cell imaging, genetic, and proteomic approaches as well as mathematical modelling. Our recent work determined how DNA replication and nuclear division are integrated during schizogony and we quantified the dynamics of nuclear multiplication throughout schizogony. This indicates that asynchronous nuclear cycles in the multinucleated schizont facilitate rapid P. falciparum proliferation. We also provide evidence that in P. falciparum early mitotic events a linked to the onset of S-phase, which may compensate for the absence of canonical cell cycle checkpoints. Together, our work on P. falciparum proliferation can highlight targets for chemotherapeutic intervention to curb malaria.

Learning Objectives: 

1. Define the unusual mode of proliferation of the malaria-causing parasite Plasmodium falciparum.

2. Discuss the advantages of P. falciparum’s unusual mode of proliferation.

3. Associate molecular determinants with specific features of P. falciparum proliferation.