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Additional file 1: Table S1. Summary of advances in studies of the different layers of regulation of circadian gene expression on a genome-wide scale.

Copyright: © 2017 Rijo-Ferreira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited., Many parasitic infections show rhythmic daily patterns. Malaria blood-stage parasites have a synchronous asexual cycle, with a coordinated cycle from the moment of invasion of the red blood cells until their bursting. This cycle lasts 24 hours or multiples of 24 hours, depending on the species, and is associated with recurrent fevers in the host. The human infectious stage of the Schistosoma mansoni parasite (known as cercariae forms) emerges from snails and swims in fresh water to infect humans by penetrating through the skin. Interestingly, the emergence of this infectious stage is rhythmic and matches the behavior of its final host: occurring during the daytime in parasites that infect humans and in the early evening in parasites that infect nocturnal rats., This work was supported by an HHMI International Early Career Scientist award (55007419, to LMF) and Fundação para a Ciência e Tecnologia award (IF/01050/2014 to LMF). JST is an Investigator in the Howard Hughes Medical Institute. FRF is a Research Associate in the Howard Hughes Medical Institute. HHMI: http://www.hhmi.org; FCT: http://www.fct.pt.

© 2015 John Wiley & Sons Ltd., The causative agent of human African trypanosomiasis, Trypanosoma brucei, lacks de novo purine biosynthesis and depends on purine salvage from the host. The purine salvage pathway is redundant and contains two routes to guanosine-5'-monophosphate (GMP) formation: conversion from xanthosine-5'-monophosphate (XMP) by GMP synthase (GMPS) or direct salvage of guanine by hypoxanthine-guanine phosphoribosyltransferase (HGPRT). We show recombinant T. brucei GMPS efficiently catalyzes GMP formation. Genetic knockout of GMPS in bloodstream parasites led to depletion of guanine nucleotide pools and was lethal. Growth of gmps null cells was only rescued by supraphysiological guanine concentrations (100 μM) or by expression of an extrachromosomal copy of GMPS. Hypoxanthine was a competitive inhibitor of guanine rescue, consistent with a common uptake/metabolic conversion mechanism. In mice, gmps null parasites were unable to establish an infection demonstrating that GMPS is essential for virulence and that plasma guanine is insufficient to support parasite purine requirements. These data validate GMPS as a potential therapeutic target for treatment of human African trypanosomiasis. The ability to strategically inhibit key metabolic enzymes in the purine pathway unexpectedly bypasses its functional redundancy by exploiting both the nature of pathway flux and the limited nutrient environment of the parasite's extracellular niche., This work was supported by National Institutes of Health grants 1R01AI078962 (to KS and MAP), 2R37AI034432 (to MAP) and GM007062 (to CL); the Welch Foundation grant I-1257 (to MAP) and Fundação para a Ciência e Tecnologia (FCT, Portugal) SFRH/BD/51286/2010 to FRF.

Malaria transmission begins when infected female Anopheles mosquitos deposit Plasmodium parasites into the mammalian host's skin during a bloodmeal. The salivary gland-resident sporozoite parasites migrate to the bloodstream, subsequently invading and replicating within hepatocytes. As Anopheles mosquitos are more active at night, with a 24-hour rhythm, we investigated whether their salivary glands are under circadian control, anticipating bloodmeals and modulating sporozoite biology for host encounters. Here we show that approximately half of the mosquito salivary gland transcriptome, particularly genes essential for efficient bloodmeals such as anti-blood clotting factors, exhibits circadian rhythmic expression. Furthermore, we demonstrate that mosquitoes prefer to feed during nighttime, with the amount of blood ingested varying cyclically throughout the day. Notably, we show a substantial subset of the sporozoite transcriptome cycling throughout the day. These include genes involved in parasite motility, potentially modulating the ability to initiate infection at different times of day. Thus, although sporozoites are typically considered quiescent, our results demonstrate their transcriptional activity, revealing robust daily rhythms of gene expression. Our findings suggest a circadian evolutionary relationship between the vector, parasite and mammalian host that together modulate malaria transmission.