Research Article

An intrinsic oscillator drives the blood stage cycle of the malaria parasite Plasmodium falciparum

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Science  15 May 2020:
Vol. 368, Issue 6492, pp. 754-759
DOI: 10.1126/science.aba4357

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Plasmodium's inner clock

Malarial fevers are notably regular, occurring when parasitized red blood cells rupture synchronously to release replicated parasites. It has long been speculated that the Plasmodium parasites that cause malaria must therefore have intrinsic circadian clocks to be able to synchronize like this. Two groups have now probed gene expression in experiments and models using data obtained during the developmental cycles of P. falciparum in vitro and in the mouse model of P. chabaudi malaria. Smith et al. discovered that four strains of P. falciparum have circadian and cell cycle oscillators, each with distinctive periodicities that can be experimentally manipulated. Rijo-Ferreira et al. found that gene expression in P. chabaudi was strikingly rhythmic, persisted during constant darkness and in infections of arrhythmic mice, and synchronized by entraining to the host's periodicity.

Science, this issue p. 754, p. 746


The blood stage of the infection of the malaria parasite Plasmodium falciparum 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 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 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 Plasmodium’s rhythmic life cycle.

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