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 Llinás, Oliver Billker, Maria M. Mota

Research output: Contribution to journalArticle

47 Scopus citations

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

All Science Journal Classification (ASJC) codes

  • General

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    Mancio-Silva, L., Slavic, K., Grilo Ruivo, M. T., Grosso, A. R., Modrzynska, K. K., Vera, I. M., Sales-Dias, J., Gomes, A. R., Macpherson, C. R., Crozet, P., Adamo, M., Baena-Gonzalez, E., Tewari, R., Llinás, M., Billker, O., & Mota, M. M. (2017). Nutrient sensing modulates malaria parasite virulence. Nature, 547(7662), 213-216. https://doi.org/10.1038/nature23009