Nutrient sensing modulates malaria parasite virulence

Mâncio-Silva, Liliana; Slavic, Ksenija; Ruivo, Margarida T. Grilo; Grosso, Ana Rita; Modrzynska, Katarzyna; Vera, Iset Medina; Sales-Dias, Joana; Gomes, Ana; MacPherson, Cameron Ross; Crozet, Pierre; Adamo, Mattia; Baena-González, Elena; Tewari, Rita; Llinás, Manuel; Billker, Oliver; Mota, Maria M.

doi:10.1038/nature23009

Cited by 162 publications

(177 citation statements)

References 39 publications

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“…In addition, blood-stage parasites have to adapt to constantly changing nutrient availability. Recent work has demonstrated that the major energy source for the parasite, glucose, is used as an environmental sensor to modulate progeny number and hence virulence via a signaling cascade 32 . Surprisingly, no effect on transmission was observed under caloric restriction, and glucose complementation did not block sexual conversion in our study 16 .…”

Section: Discussionmentioning

confidence: 99%

Probing Plasmodium falciparum sexual commitment at the single-cell level

Brancucci¹,

Niz²,

Straub³

et al. 2018

Wellcome Open Res

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Background: Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in Plasmodium falciparum. Parasites have to make this essential life-cycle decision in preparation for human-to-mosquito transmission. Methods: By combining transcriptional profiling with quantitative imaging and genetics, we defined a transcriptional signature in sexually committed cells. Results: We found this transcriptional signature to be distinct from general changes in parasite metabolism that can be observed in response to commitment-inducing conditions. Conclusions: This proof-of-concept study provides a template to capture transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign.

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Section: Discussionmentioning

confidence: 99%

Probing Plasmodium falciparum sexual commitment at the single-cell level

Brancucci¹,

Niz²,

Straub³

et al. 2018

Wellcome Open Res

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“…The maturation of the parasite has also recently been classified based on the transcriptome . Perturbation of the malaria life cycle has now been demonstrated in response to nutrient deprivation, drug treatment, drug resistance, host innate immunity and nutritional status . Given the increasing observation of Plasmodium parasites with altered development within RBCs, advancing models to understand the molecular underpinnings of parasite development and how it is perturbed, is likely to have broad applications.…”

Section: Host Control Of Parasite Proliferationmentioning

confidence: 99%

Within‐host modeling of blood‐stage malaria

Khoury

Aogo

Randriafanomezantsoa‐Radohery

et al. 2018

Immunological Reviews

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Malaria infection continues to be a major health problem worldwide and drug resistance in the major human parasite species, Plasmodium falciparum, is increasing in South East Asia. Control measures including novel drugs and vaccines are in development, and contributions to the rational design and optimal usage of these interventions are urgently needed. Infection involves the complex interaction of parasite dynamics, host immunity, and drug effects. The long life cycle (48 hours in the common human species) and synchronized replication cycle of the parasite population present significant challenges to modeling the dynamics of Plasmodium infection. Coupled with these, variation in immune recognition and drug action at different life cycle stages leads to further complexity. We review the development and progress of "within-host" models of Plasmodium infection, and how these have been applied to understanding and interpreting human infection and animal models of infection.

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“…Given that completing the IDC is glucose demanding, malaria parasites may be expected to express genes rhythmically to utilize the energy source efficiently. This could be achieved via the recently discovered nutrient sensing mechanism and that allows parasites to respond to alterations in glucose availability through transcriptional rearrangement 27 . In support of this, genes involved in energy metabolism pathways (glycolysis, fructose and mannose metabolism) showed circadian transcription patterns in the matched parasites while this rhythmicity was lost in mismatched parasites ( Figs.…”

Section: Energy Metabolismmentioning

confidence: 99%

Disruption of the coordination between host circadian rhythms and malaria parasite development alters the duration of the intraerythrocytic cycle

Subudhi

O’Donnell

Ramaprasad

et al. 2019

Preprint

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Malaria parasites complete their intra-erythrocytic developmental cycle (IDC) in multiples of 24 hours (depending on the species), suggesting a circadian basis to the asexual cell cycle, but the mechanism controlling this periodicity is unknown.Combining in vivo and in vitro approaches using rodent and human malaria parasites, we reveal that: (i) 57% of Plasmodium chabaudi genes exhibit 24 h "circadian" periodicity in transcription; (ii) 58% of these genes lose transcriptional rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 9% of Plasmodium falciparum genes show circadian transcription under free-running conditions; (iv) Serpentine receptor 10 (SR10) has a circadian transcription profile and disrupting it in rodent malaria parasites shortens the IDC by 2-3 hours; (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 show that malaria parasites are at least partly responsible for scheduling their IDCs explaining the fitness benefits of coordination with host rhythms.Daily fluctuations in environmental parameters such as light and temperature are assumed to select for the evolution of circadian clocks. In many organisms, circadian RESULTSThe transcriptome of Plasmodium chabaudi responds to host circadian rhythms Transcriptome analyses of time series RNA sequencing datasets were performed with P.chabaudi parasites from infections that were in synchrony (phase aligned; "host rhythm matched") and out of synchrony (out of phase; "host rhythm mismatched") with host circadian rhythms (for details see methods section). Briefly, a controlled number of infected red blood cells (RBC) were sub-inoculated from donor mice into two groups of recipient mice (n = 43 per group) each housed under different light regimes (12 hours (h)

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Nutrient sensing modulates malaria parasite virulence

Cited by 162 publications

References 39 publications

Probing Plasmodium falciparum sexual commitment at the single-cell level

Probing Plasmodium falciparum sexual commitment at the single-cell level

Within‐host modeling of blood‐stage malaria

Disruption of the coordination between host circadian rhythms and malaria parasite development alters the duration of the intraerythrocytic cycle

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