An Intrinsic Oscillator Drives the Blood Stage Cycle of the Malaria Parasite, Plasmodium falciparum

Abstract

The blood-stage infection of the malaria parasite, Plasmodium falciparum, exhibits ts a48-hour developmental cycle that culminates in the synchronous release of parasites from red blood cells, triggering 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 hypotheses, we examined the P. falciparum cycle in an in vitro culture system and show that the parasite has molecular signatures associated with circadian and cell-cycle oscillators. Each of four strains examined has a unique period, indicating 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 Plasmodium’s rhythmic life cycle.

One Sentence Summary:

Periodicity of the malaria parasite does not require rhythmic cues from the host, but rather from an intrinsic parasite oscillator.