Nutrient sensing modulates malaria parasite virulence

Liliana Mancio-Silva, Ksenija Slavic, Margarida T. Grilo Ruivo, Ana Rita Grosso, Katarzyna K. Modrzynska, Iset Medina Vera, Joana Sales-Dias, Ana Rita Gomes, Cameron Ross Macpherson, Pierre Crozet, Mattia Adamo, Elena Baena-Gonzalez, Rita Tewari, Manuel Llinas, Oliver Billker, Maria M. Mota

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The lifestyle of intracellular pathogens, such as malaria parasites, is intimately connected to that of their host, primarily for nutrient supply. Nutrients act not only as primary sources of energy but also as regulators of gene expression, metabolism and growth, through various signalling networks that enable cells to sense and adapt to varying environmental conditions. Canonical nutrient-sensing pathways are presumed to be absent from the causative agent of malaria, Plasmodium, thus raising the question of whether these parasites can sense and cope with fluctuations in host nutrient levels. Here we show that Plasmodium blood-stage parasites actively respond to host dietary calorie alterations through rearrangement of their transcriptome accompanied by substantial adjustment of their multiplication rate. A kinome analysis combined with chemical and genetic approaches identified KIN as a critical regulator that mediates sensing of nutrients and controls a transcriptional response to the host nutritional status. KIN shares homology with SNF1/AMPKα, and yeast complementation studies suggest that it is part of a functionally conserved cellular energy-sensing pathway. Overall, these findings reveal a key parasite nutrient-sensing mechanism that is critical for modulating parasite replication and virulence.

Original languageEnglish (US)
Pages (from-to)213-216
Number of pages4
JournalNature
Volume547
Issue number7662
DOIs
StatePublished - Jul 13 2017

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Malaria
Virulence
Parasites
Food
Plasmodium malariae
Social Adjustment
AMP-Activated Protein Kinases
Plasmodium
Regulator Genes
Nutritional Status
Transcriptome
Life Style
Yeasts
Gene Expression
Growth

All Science Journal Classification (ASJC) codes

  • General

Cite this

Mancio-Silva, L., Slavic, K., Grilo Ruivo, M. T., Grosso, A. R., Modrzynska, K. K., Vera, I. M., ... Mota, M. M. (2017). Nutrient sensing modulates malaria parasite virulence. Nature, 547(7662), 213-216. https://doi.org/10.1038/nature23009
Mancio-Silva, Liliana ; Slavic, Ksenija ; Grilo Ruivo, Margarida T. ; Grosso, Ana Rita ; Modrzynska, Katarzyna K. ; Vera, Iset Medina ; Sales-Dias, Joana ; Gomes, Ana Rita ; Macpherson, Cameron Ross ; Crozet, Pierre ; Adamo, Mattia ; Baena-Gonzalez, Elena ; Tewari, Rita ; Llinas, Manuel ; Billker, Oliver ; Mota, Maria M. / Nutrient sensing modulates malaria parasite virulence. In: Nature. 2017 ; Vol. 547, No. 7662. pp. 213-216.
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Mancio-Silva, L, Slavic, K, Grilo Ruivo, MT, Grosso, AR, Modrzynska, KK, Vera, IM, Sales-Dias, J, Gomes, AR, Macpherson, CR, Crozet, P, Adamo, M, Baena-Gonzalez, E, Tewari, R, Llinas, M, Billker, O & Mota, MM 2017, 'Nutrient sensing modulates malaria parasite virulence', Nature, vol. 547, no. 7662, pp. 213-216. https://doi.org/10.1038/nature23009

Nutrient sensing modulates malaria parasite virulence. / Mancio-Silva, Liliana; Slavic, Ksenija; Grilo Ruivo, Margarida T.; Grosso, Ana Rita; Modrzynska, Katarzyna K.; Vera, Iset Medina; Sales-Dias, Joana; Gomes, Ana Rita; Macpherson, Cameron Ross; Crozet, Pierre; Adamo, Mattia; Baena-Gonzalez, Elena; Tewari, Rita; Llinas, Manuel; Billker, Oliver; Mota, Maria M.

In: Nature, Vol. 547, No. 7662, 13.07.2017, p. 213-216.

Research output: Contribution to journalArticle

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AU - Mancio-Silva, Liliana

AU - Slavic, Ksenija

AU - Grilo Ruivo, Margarida T.

AU - Grosso, Ana Rita

AU - Modrzynska, Katarzyna K.

AU - Vera, Iset Medina

AU - Sales-Dias, Joana

AU - Gomes, Ana Rita

AU - Macpherson, Cameron Ross

AU - Crozet, Pierre

AU - Adamo, Mattia

AU - Baena-Gonzalez, Elena

AU - Tewari, Rita

AU - Llinas, Manuel

AU - Billker, Oliver

AU - Mota, Maria M.

PY - 2017/7/13

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N2 - The lifestyle of intracellular pathogens, such as malaria parasites, is intimately connected to that of their host, primarily for nutrient supply. Nutrients act not only as primary sources of energy but also as regulators of gene expression, metabolism and growth, through various signalling networks that enable cells to sense and adapt to varying environmental conditions. Canonical nutrient-sensing pathways are presumed to be absent from the causative agent of malaria, Plasmodium, thus raising the question of whether these parasites can sense and cope with fluctuations in host nutrient levels. Here we show that Plasmodium blood-stage parasites actively respond to host dietary calorie alterations through rearrangement of their transcriptome accompanied by substantial adjustment of their multiplication rate. A kinome analysis combined with chemical and genetic approaches identified KIN as a critical regulator that mediates sensing of nutrients and controls a transcriptional response to the host nutritional status. KIN shares homology with SNF1/AMPKα, and yeast complementation studies suggest that it is part of a functionally conserved cellular energy-sensing pathway. Overall, these findings reveal a key parasite nutrient-sensing mechanism that is critical for modulating parasite replication and virulence.

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Mancio-Silva L, Slavic K, Grilo Ruivo MT, Grosso AR, Modrzynska KK, Vera IM et al. Nutrient sensing modulates malaria parasite virulence. Nature. 2017 Jul 13;547(7662):213-216. https://doi.org/10.1038/nature23009