An intrinsic oscillator drives the blood stage cycle of the malaria parasite <i>Plasmodium falciparum</i>.

Abstract

The blood stage of the infection of the malaria parasite <i>Plasmodium falciparum</i> exhibits a 48-hour developmental cycle that culminates in the synchronous release of parasites from red blood cells, which triggers 48-hour fever cycles in the host. This cycle could be driven extrinsically by host circadian processes or by a parasite-intrinsic oscillator. To distinguish between these hypotheses, we examine the <i>P. falciparum</i> cycle in an in vitro culture system and show that the parasite has molecular signatures associated with circadian and cell cycle oscillators. Each of the four strains examined has a different period, which indicates strain-intrinsic period control. Finally, we demonstrate that parasites have low cell-to-cell variance in cycle period, on par with a circadian oscillator. We conclude that an intrinsic oscillator maintains <i>Plasmodium</i>'s rhythmic life cycle.