title: Trypanosoma brucei metabolism is under circadian control.
abstract: The Earth's rotation forced life to evolve under cyclic day and night environmental changes. To anticipate such daily cycles, prokaryote and eukaryote free-living organisms evolved intrinsic clocks that regulate physiological and behavioural processes. Daily rhythms have been observed in organisms living within hosts, such as parasites. Whether parasites have intrinsic molecular clocks or whether they simply respond to host rhythmic physiological cues remains unknown. Here, we show that Trypanosoma brucei, the causative agent of human sleeping sickness, has an intrinsic circadian clock that regulates its metabolism in two different stages of the life cycle. We found that, in vitro, ∼10% of genes in T. brucei are expressed with a circadian rhythm. The maximum expression of these genes occurs at two different phases of the day and may depend on a post-transcriptional mechanism. Circadian genes are enriched in cellular metabolic pathways and coincide with two peaks of intracellular adenosine triphosphate concentration. Moreover, daily changes in the parasite population lead to differences in suramin sensitivity, a drug commonly used to treat this infection. These results demonstrate that parasites have an intrinsic circadian clock that is independent of the host, and which regulates parasite biology throughout the day.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.|Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111, USA.|Graduate Program in Areas of Basic and Applied Biology, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4099-002 Porto, Portugal.
authors.forename: Filipa
authors.identifier: http://orcid.org/0000-0002-4003-020X
authors.initials: F
authors.lastname: Rijo-Ferreira
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pinto-Neves
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Nuno L
authors.initials: NL
authors.lastname: Barbosa-Morais
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111, USA.|Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9111, USA.
authors.forename: Joseph S
authors.identifier: http://orcid.org/0000-0003-0384-8878
authors.initials: JS
authors.lastname: Takahashi
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Luisa M
authors.identifier: http://orcid.org/0000-0002-5752-6586
authors.initials: LM
authors.lastname: Figueiredo
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D002940:Circadian Rhythm; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008660:Metabolism; D021261:Parasitic Sensitivity Tests; D013498:Suramin / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*
chemical_list: D014344:Trypanocidal Agents; D013498:Suramin; D000255:Adenosine Triphosphate