Mancio-Silva, L. et al. (2017) Nutrient sensing modulates malaria parasite virulence. Nature, 547(7662), pp. 213-216. (doi: 10.1038/nature23009) (PMID:28678779) (PMCID:PMC5511512)
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162929.pdf - Accepted Version 4MB |
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.
Item Type: | Articles (Letter) |
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Additional Information: | The work was supported by European Research Council (311502) and Fundação para a Ciência e Tecnologia (FCT) grants (EXCL/IMI-MIC/0056/2012) and (PTDC/SAU-MET/118199/2010) to M.M.M. and L.M.S., respectively. L.M.S., A.R.Go. and M.M.M. were supported by the European Commission (FP7/2007-2013; EVIMALAR 242095). L.M.S. was supported by EMBO LTF (ALTF 960-2009). K.S. was sponsored by FCT fellowship (SFRH/BPD/111788/2015). I.M.V. received EMBO (LTF 712-2012) and NIH NRSA (5F32AI104252-03) fellowships. Work at the Sanger Institute was funded by Wellcome Trust (098051) and Medical Research Council (MRC, G0501670). Work at the Instituto Gulbenkian de Ciência was funded through FCT grants (SFRH-BPD79255-2011 and UID/Multi/04551/2013). R.T. was supported by MRC grant (G0900109, MR/K011782/1). M.L. was funded through the Burroughs Wellcome Fund and the NIH Director’s New Innovators award (1DP2OD001315-01). |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Modrzynska, Dr Katarzyna |
Authors: | 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., and Mota, M. M. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Nature |
Publisher: | Nature Publishing Group |
ISSN: | 0028-0836 |
ISSN (Online): | 1476-4687 |
Copyright Holders: | Copyright © 2017 Macmillan Publishers Limited, part of Springer Nature |
First Published: | First published in Nature 547(7662):213-216 |
Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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