Editors' ChoiceCIRCADIAN REGULATION

Can eating help treat malaria?

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Science Translational Medicine  16 Sep 2020:
Vol. 12, Issue 561, eabe1716
DOI: 10.1126/scitranslmed.abe1716

Abstract

The identification of metabolic control of the Plasmodium life cycle may open novel avenues for malaria treatment.

The alignment of pathogen and host biological cycles directly affects both the virulence of the pathogen and the defenses of the host. An archetypical example of this tug of war is the balance between the life cycle of Plasmodium, the parasite that causes malaria, and the host’s daily biological rhythms. Plasmodium coordinates with daily host rhythms to time the production of its asexual, transmissive form. Consequently, the proper timing of treatment with respect to the Plasmodium life cycle could have significant effects on efficacy. However, it was not known whether the life cycle of Plasmodium used the host’s circadian clock as a timing mechanism or whether the metabolic cues of host fasting and feeding controlled Plasmodium asexual reproduction.

To determine the role of the host clock in the Plasmodium life cycle, O’Donnell et al. subjected wild-type and circadian clock knock-out mice to either time-restricted or continuous feeding protocols. They found that regardless of the genotype, Plasmodium asexual reproduction oscillated only in organisms with a fasting-feeding rhythm, suggesting that the host circadian clock is not essential for coordinating the Plasmodium life cycle. Conversely, when O’Donnell et al. investigated parasite load, they found that the number of parasites infecting the host was significantly decreased in clock knock-out mice as compared to wild-type, demonstrating that the circadian clock may negatively affect the host response to Plasmodium.

The molecular mechanism that coordinates the Plasmodium life cycle to host metabolic rhythms remains unclear. Because organisms without a circadian clock can also display 24-hour biological rhythms when under a time-restricted feeding protocol and the mechanisms that control 24-hour Plasmodium rhythms are poorly understood, identifying the source of this coordination will be complicated. However, the discovery that fasting-feeding cycles regulate the Plasmodium life cycle suggests that feeding protocols could increase treatment efficacy for a disease that yearly kills half a million people.

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