Journal article
Legionella pneumophila S1P-lyase targets host sphingolipid metabolism and restrains autophagy
M Rolando, P Escoll, T Nora, J Botti, V Boitez, C Bedia, C Daniels, G Abraham, PJ Stogios, T Skarina, C Christophe, D Dervins-Ravault, C Cazalet, H Hilbi, TWT Rupasinghe, D Tull, MJ McConville, SY Ong, EL Hartland, P Codogno Show all
Proceedings of the National Academy of Sciences of the United States of America | Published : 2016
Abstract
Autophagy is an essential component of innate immunity, enabling the detection and elimination of intracellular pathogens. Legionella pneumophila, an intracellular pathogen that can cause a severe pneumonia in humans, is able to modulate autophagy through the action of effector proteins that are translocated into the host cell by the pathogen's Dot/Icm type IV secretion system. Many of these effectors share structural and sequence similarity with eukaryotic proteins. Indeed, phylogenetic analyses have indicated their acquisition by horizontal gene transfer from a eukaryotic host. Here we report that L. pneumophila translocates the effector protein sphingosine-1 phosphate lyase (LpSpl) to tar..
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Awarded by Agència de Gestió d'Ajuts Universitaris i de Recerca
Funding Acknowledgements
We thank G. Pfaffinger for D. discoideum infection, L. Eichinger for ATG9<SUP>-/-</SUP> D. discoideum, and the Imagopole-CiTech (part of the FranceBioImaging infrastructure supported by ANR-10-INSB-04-01, Conseil de la Region Ile-de-France, Fondation pour la Recherche Medicale). C. Buchrieser was funded by the Institut Pasteur, Domaine d'Interet Majeur Malinf Grant ANR-10-LABX-62-IBEID, and Infect-European Research Area (ERA) project EUGENPATH (ANR-13-IFEC-0003-02); P.E. was funded by Fondation pour la Recherche Medicale (FRM) Grant DEQ20120323697; C. Bedia was funded by a fellowship from Agencia de Gestio d'Ajuts Universitaris i Recerca, Generalitat de Catalunya; H.H. was funded by the University of Zurich, the Swiss National Science Foundation (31003A_153200), and the Bundesministerium fur Bildung und Forschung (Infect-ERA project EUGENPATH, 031A410A). The crystal structure was solved in part by National Institutes of Health Grants GM074942 and GM094585 (to A.S. through Midwest Center for Structural Genomics) and by the US Department of Energy, Office of Biological and Environmental Research, under Contract DE-AC02-06CH11357. The P.C. and T.L. laboratories were supported by INSERM.