The Malaria Parasite Has an Intrinsic Clock

Overview

Journal Science

Specialty Science

Date 2020 May 16

PMID 32409471

Citations 41

Authors

Filipa Rijo-Ferreira

Victoria A Acosta-Rodriguez

John H Abel

Izabela Kornblum

Ines Bento

Gokhul Kilaru

Elizabeth B Klerman

Maria M Mota

Joseph S Takahashi

Affiliations

Soon will be listed here.

Abstract

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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References

van der Horst G, Muijtjens M, Kobayashi K, Takano R, Kanno S, Takao M . Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. Nature. 1999; 398(6728):627-30. DOI: 10.1038/19323. View

Rijo-Ferreira F, Takahashi J, Figueiredo L . Circadian rhythms in parasites. PLoS Pathog. 2017; 13(10):e1006590. PMC: 5638552. DOI: 10.1371/journal.ppat.1006590. View

Hirako I, Assis P, Hojo-Souza N, Reed G, Nakaya H, Golenbock D . Daily Rhythms of TNFα Expression and Food Intake Regulate Synchrony of Plasmodium Stages with the Host Circadian Cycle. Cell Host Microbe. 2018; 23(6):796-808.e6. PMC: 6014587. DOI: 10.1016/j.chom.2018.04.016. View

Jones M, Hill M, Hope A . The circadian flight activity of the mosquito Anopheles Gambiae: phase setting by the light régime. J Exp Biol. 1967; 47(3):503-11. DOI: 10.1242/jeb.47.3.503. View

Fougere A, Jackson A, Bechtsi D, Braks J, Annoura T, Fonager J . Variant Exported Blood-Stage Proteins Encoded by Plasmodium Multigene Families Are Expressed in Liver Stages Where They Are Exported into the Parasitophorous Vacuole. PLoS Pathog. 2016; 12(11):e1005917. PMC: 5113031. DOI: 10.1371/journal.ppat.1005917. View

Kondo T, Mori T, Lebedeva N, Aoki S, Ishiura M, Golden S . Circadian rhythms in rapidly dividing cyanobacteria. Science. 1997; 275(5297):224-7. DOI: 10.1126/science.275.5297.224. View

Hoo R, Zhu L, Amaladoss A, Mok S, Natalang O, Lapp S . Integrated analysis of the Plasmodium species transcriptome. EBioMedicine. 2016; 7:255-66. PMC: 4909483. DOI: 10.1016/j.ebiom.2016.04.011. View

Siepka S, Yoo S, Park J, Song W, Kumar V, Hu Y . Circadian mutant Overtime reveals F-box protein FBXL3 regulation of cryptochrome and period gene expression. Cell. 2007; 129(5):1011-23. PMC: 3762874. DOI: 10.1016/j.cell.2007.04.030. View

Cambie G, Landau I, CHABAUD A . [Timing niches of 3 species of Plasmodium coexisting in a rodent in Central Africa]. C R Acad Sci III. 1990; 310(5):183-8. View

10.

Koike N, Yoo S, Huang H, Kumar V, Lee C, Kim T . Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. Science. 2012; 338(6105):349-54. PMC: 3694775. DOI: 10.1126/science.1226339. View

11.

Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong E, Gill S . Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 2012; 15(6):848-60. PMC: 3491655. DOI: 10.1016/j.cmet.2012.04.019. View

12.

Gonze D, Bernard S, Waltermann C, Kramer A, Herzel H . Spontaneous synchronization of coupled circadian oscillators. Biophys J. 2005; 89(1):120-9. PMC: 1366510. DOI: 10.1529/biophysj.104.058388. View

13.

Deharo E, Coquelin F, CHABAUD A, Landau I . The erythrocytic schizogony of two synchronized strains of plasmodium berghei, NK65 and ANKA, in normocytes and reticulocytes. Parasitol Res. 1996; 82(2):178-82. DOI: 10.1007/s004360050091. View

14.

Le Roch K, Zhou Y, Blair P, Grainger M, Moch J, Haynes J . Discovery of gene function by expression profiling of the malaria parasite life cycle. Science. 2003; 301(5639):1503-8. DOI: 10.1126/science.1087025. View

15.

Acosta-Rodriguez V, de Groot M, Rijo-Ferreira F, Green C, Takahashi J . Mice under Caloric Restriction Self-Impose a Temporal Restriction of Food Intake as Revealed by an Automated Feeder System. Cell Metab. 2017; 26(1):267-277.e2. PMC: 5576447. DOI: 10.1016/j.cmet.2017.06.007. View

16.

Bell-Pedersen D, Cassone V, Earnest D, Golden S, Hardin P, Thomas T . Circadian rhythms from multiple oscillators: lessons from diverse organisms. Nat Rev Genet. 2005; 6(7):544-56. PMC: 2735866. DOI: 10.1038/nrg1633. View

17.

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W . limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. PMC: 4402510. DOI: 10.1093/nar/gkv007. View

18.

Yang R, Su Z . Analyzing circadian expression data by harmonic regression based on autoregressive spectral estimation. Bioinformatics. 2010; 26(12):i168-74. PMC: 2881374. DOI: 10.1093/bioinformatics/btq189. View

19.

Thaben P, Westermark P . Detecting rhythms in time series with RAIN. J Biol Rhythms. 2014; 29(6):391-400. PMC: 4266694. DOI: 10.1177/0748730414553029. View

20.

Rijo-Ferreira F, Carvalho T, Afonso C, Sanches-Vaz M, Costa R, Figueiredo L . Sleeping sickness is a circadian disorder. Nat Commun. 2018; 9(1):62. PMC: 5754353. DOI: 10.1038/s41467-017-02484-2. View