Background: The phylum Apicomplexa includes intracellular parasites causing immense global disease burden, the
deadliest of them being the human malaria parasite Plasmodium falciparum, which invades and replicates within
erythrocytes. The cytoskeletal protein actin is well conserved within apicomplexans but divergent from mammalian actins,
and was primarily reported to function during host cell invasion. However, novel invasion mechanisms have been described
for several apicomplexans, and specific functions of the acto-myosin system are being reinvestigated. Of the two actin
genes in P. falciparum, actin-1 (pfact1) is ubiquitously expressed in all life-cycle stages and is thought to be required for
erythrocyte invasion, although its functions during parasite development are unknown, and definitive in vivo
characterisation during invasion is lacking.
Results: Here we have used a conditional Cre-lox system to investigate the functions of PfACT1 during P. falciparum bloodstage
development and host cell invasion. We demonstrate that PfACT1 is crucially required for segregation of the plastid-like
organelle, the apicoplast, and for efficient daughter cell separation during the final stages of cytokinesis. Surprisingly, we observe
that egress from the host cell is not an actin-dependent process. Finally, we show that parasites lacking PfACT1 are capable of
microneme secretion, attachment and formation of a junction with the erythrocyte, but are incapable of host cell invasion.
Conclusions: This study provides important mechanistic insights into the definitive essential functions of PfACT1 in
P. falciparum, which are not only of biological interest, but owing to functional divergence from mammalian actins,
could also form the basis for the development of novel therapeutics against apicomplexans.