Research Article

The malaria parasite has an intrinsic clock

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Science  15 May 2020:
Vol. 368, Issue 6492, pp. 746-753
DOI: 10.1126/science.aba2658

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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


Malarial rhythmic fevers are the consequence of the synchronous bursting of red blood cells (RBCs) on completion of the malaria parasite asexual cell cycle. Here, we hypothesized that an intrinsic clock in the parasite Plasmodium chabaudi underlies the 24-hour-based rhythms of RBC bursting in mice. We show that parasite rhythms are flexible and lengthen to match the rhythms of hosts with long circadian periods. We also show that malaria rhythms persist even when host food intake is evenly spread across 24 hours, suggesting that host feeding cues are not required for synchrony. Moreover, we find that the parasite population remains synchronous and rhythmic even in an arrhythmic clock mutant host. Thus, we propose that parasite rhythms are generated by the parasite, possibly to anticipate its circadian environment.

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