The malaria parasite has an intrinsic clock

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 underlies the 24-hour-based rhythms of RBC bursting in mice. We show that parasit...

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Published inScience (American Association for the Advancement of Science) Vol. 368; no. 6492; pp. 746 - 753
Main Authors Rijo-Ferreira, Filipa, Acosta-Rodriguez, Victoria A, Abel, John H, Kornblum, Izabela, Bento, Ines, Kilaru, Gokhul, Klerman, Elizabeth B, Mota, Maria M, Takahashi, Joseph S
Format Journal Article
LanguageEnglish
Published United States The American Association for the Advancement of Science 15.05.2020
Subjects
Animal models
Animals
Biological clocks
Bursting
Cell cycle
Circadian rhythm
Circadian Rhythm - genetics
Circadian Rhythm - physiology
Circadian rhythms
CLOCK Proteins - genetics
Cues
Darkness
Eating
Erythrocytes
Erythrocytes - parasitology
Feeding Behavior
Fever - parasitology
Fever - physiopathology
Food intake
Gene expression
Gene Expression Regulation
Host-Parasite Interactions - genetics
Host-Parasite Interactions - physiology
Malaria
Malaria - parasitology
Malaria - physiopathology
Mice
Mice, Mutant Strains
Oscillators
Parasites
Periodicity
Plasmodium chabaudi
Plasmodium chabaudi - genetics
Plasmodium chabaudi - physiology
Plasmodium falciparum
Transcription, Genetic
Vector-borne diseases
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Summary: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 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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Author contributions: F.R.-F. and J.S.T. conceptualized and led the study. F.R.-F performed the experiments and data analysis. I.B. contributed to the clock homology search and assisted on the WTLD experiment and V.A.R. assisted on all the other experiments and contributed to the behavior analysis. J.H.A. designed the mathematical model and contributed to data analysis. I.K. prepared many of the samples for sequencing and qPCR and assessed parasitemias. G.K. mapped sequencing reads and assisted with motif search analysis. F.R.-F., V.A.R., I.B., J.H.A., M.M.M. and J.S.T participated in the interpretation of the data. F.R.-F. wrote the manuscript. F.R.-F., V.A.R., I.B., J.H.A., E.B.K., M.M.M. and J.S.T revised it and all authors approved it
contributed equally to this project
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aba2658