Glutamate utilization couples oxidative stress defense and the tricarboxylic acid cycle in Francisella phagosomal escape.

Intracellular bacterial pathogens have developed a variety of strategies to avoid degradation by the host innate immune defense mechanisms triggered upon phagocytocis. Upon infection of mammalian host cells, the intracellular pathogen Francisella replicates exclusively in the cytosolic compartment....

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Autores principales:	Elodie Ramond, Gael Gesbert, Mélanie Rigard, Julien Dairou, Marion Dupuis, Iharilalao Dubail, Karin Meibom, Thomas Henry, Monique Barel, Alain Charbit
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ca9c6d9a8fcd4e988e24149e35d7aacf
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spelling	oai:doaj.org-article:ca9c6d9a8fcd4e988e24149e35d7aacf2021-11-18T06:07:05ZGlutamate utilization couples oxidative stress defense and the tricarboxylic acid cycle in Francisella phagosomal escape.1553-73661553-737410.1371/journal.ppat.1003893https://doaj.org/article/ca9c6d9a8fcd4e988e24149e35d7aacf2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24453979/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Intracellular bacterial pathogens have developed a variety of strategies to avoid degradation by the host innate immune defense mechanisms triggered upon phagocytocis. Upon infection of mammalian host cells, the intracellular pathogen Francisella replicates exclusively in the cytosolic compartment. Hence, its ability to escape rapidly from the phagosomal compartment is critical for its pathogenicity. Here, we show for the first time that a glutamate transporter of Francisella (here designated GadC) is critical for oxidative stress defense in the phagosome, thus impairing intra-macrophage multiplication and virulence in the mouse model. The gadC mutant failed to efficiently neutralize the production of reactive oxygen species. Remarkably, virulence of the gadC mutant was partially restored in mice defective in NADPH oxidase activity. The data presented highlight links between glutamate uptake, oxidative stress defense, the tricarboxylic acid cycle and phagosomal escape. This is the first report establishing the role of an amino acid transporter in the early stage of the Francisella intracellular lifecycle.Elodie RamondGael GesbertMélanie RigardJulien DairouMarion DupuisIharilalao DubailKarin MeibomThomas HenryMonique BarelAlain CharbitPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 1, p e1003893 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Elodie Ramond Gael Gesbert Mélanie Rigard Julien Dairou Marion Dupuis Iharilalao Dubail Karin Meibom Thomas Henry Monique Barel Alain Charbit Glutamate utilization couples oxidative stress defense and the tricarboxylic acid cycle in Francisella phagosomal escape.
description	Intracellular bacterial pathogens have developed a variety of strategies to avoid degradation by the host innate immune defense mechanisms triggered upon phagocytocis. Upon infection of mammalian host cells, the intracellular pathogen Francisella replicates exclusively in the cytosolic compartment. Hence, its ability to escape rapidly from the phagosomal compartment is critical for its pathogenicity. Here, we show for the first time that a glutamate transporter of Francisella (here designated GadC) is critical for oxidative stress defense in the phagosome, thus impairing intra-macrophage multiplication and virulence in the mouse model. The gadC mutant failed to efficiently neutralize the production of reactive oxygen species. Remarkably, virulence of the gadC mutant was partially restored in mice defective in NADPH oxidase activity. The data presented highlight links between glutamate uptake, oxidative stress defense, the tricarboxylic acid cycle and phagosomal escape. This is the first report establishing the role of an amino acid transporter in the early stage of the Francisella intracellular lifecycle.
format	article
author	Elodie Ramond Gael Gesbert Mélanie Rigard Julien Dairou Marion Dupuis Iharilalao Dubail Karin Meibom Thomas Henry Monique Barel Alain Charbit
author_facet	Elodie Ramond Gael Gesbert Mélanie Rigard Julien Dairou Marion Dupuis Iharilalao Dubail Karin Meibom Thomas Henry Monique Barel Alain Charbit
author_sort	Elodie Ramond
title	Glutamate utilization couples oxidative stress defense and the tricarboxylic acid cycle in Francisella phagosomal escape.
title_short	Glutamate utilization couples oxidative stress defense and the tricarboxylic acid cycle in Francisella phagosomal escape.
title_full	Glutamate utilization couples oxidative stress defense and the tricarboxylic acid cycle in Francisella phagosomal escape.
title_fullStr	Glutamate utilization couples oxidative stress defense and the tricarboxylic acid cycle in Francisella phagosomal escape.
title_full_unstemmed	Glutamate utilization couples oxidative stress defense and the tricarboxylic acid cycle in Francisella phagosomal escape.
title_sort	glutamate utilization couples oxidative stress defense and the tricarboxylic acid cycle in francisella phagosomal escape.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ca9c6d9a8fcd4e988e24149e35d7aacf
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Glutamate utilization couples oxidative stress defense and the tricarboxylic acid cycle in Francisella phagosomal escape.

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