Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms

Amit K. Subudhi, Aidan J. O’Donnell, Abhinay Ramaprasad, Hussein M. Abkallo, Abhinav Kaushik, Hifzur R. Ansari, Alyaa M. Abdel-Haleem, Fathia Rached, Osamu Kaneko, Richard Culleton (), Sarah E. Reece () and Arnab Pain ()
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Amit K. Subudhi: King Abdullah University of Science and Technology (KAUST)
Aidan J. O’Donnell: University of Edinburgh
Abhinay Ramaprasad: King Abdullah University of Science and Technology (KAUST)
Hussein M. Abkallo: Nagasaki University
Abhinav Kaushik: King Abdullah University of Science and Technology (KAUST)
Hifzur R. Ansari: King Abdullah University of Science and Technology (KAUST)
Alyaa M. Abdel-Haleem: King Abdullah University of Science and Technology (KAUST)
Fathia Rached: King Abdullah University of Science and Technology (KAUST)
Osamu Kaneko: Nagasaki University
Richard Culleton: Nagasaki University
Sarah E. Reece: University of Edinburgh
Arnab Pain: King Abdullah University of Science and Technology (KAUST)

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Malaria parasites complete their intra-erythrocytic developmental cycle (IDC) in multiples of 24 h suggesting a circadian basis, but the mechanism controlling this periodicity is unknown. Combining in vivo and in vitro approaches utilizing rodent and human malaria parasites, we reveal that: (i) 57% of Plasmodium chabaudi genes exhibit daily rhythms in transcription; (ii) 58% of these genes lose transcriptional rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 6% of Plasmodium falciparum genes show 24 h rhythms in expression under free-running conditions; (iv) Serpentine receptor 10 (SR10) has a 24 h transcriptional rhythm and disrupting it in rodent malaria parasites shortens the IDC by 2-3 h; (v) Multiple processes including DNA replication, and the ubiquitin and proteasome pathways, are affected by loss of coordination with host rhythms and by disruption of SR10. Our results reveal malaria parasites are at least partly responsible for scheduling the IDC and coordinating their development with host daily rhythms.

Date: 2020
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DOI: 10.1038/s41467-020-16593-y

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