title: Gluconeogenesis, an essential metabolic pathway for pathogenic Francisella.
abstract: Intracellular multiplication and dissemination of the infectious bacterial pathogen Francisella tularensis implies the utilization of multiple host-derived nutrients. Here, we demonstrate that gluconeogenesis constitutes an essential metabolic pathway in Francisella pathogenesis. Indeed, inactivation of gene glpX, encoding the unique fructose 1,6-bisphosphatase of Francisella, severely impaired bacterial intracellular multiplication when cells were supplemented by gluconeogenic substrates such as glycerol or pyruvate. The ΔglpX mutant also showed a severe virulence defect in the mouse model, confirming the importance of this pathway during the in vivo life cycle of the pathogen. Isotopic profiling revealed the major role of the Embden-Meyerhof (glycolysis) pathway in glucose catabolism in Francisella and confirmed the importance of glpX in gluconeogenesis. Altogether, the data presented suggest that gluconeogenesis allows Francisella to cope with the limiting glucose availability it encounters during its infectious cycle by relying on host amino acids. Hence, targeting the gluconeogenic pathway might constitute an interesting therapeutic approach against this pathogen.
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche, Paris, France.|INSERM U1151 - CNRS UMR 8253, Institut Necker-Enfants Malades, Equipe 11: Pathogénie des Infections Systémiques, Paris, France.
authors.forename: Terry
authors.initials: T
authors.lastname: Brissac
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche, Paris, France.|INSERM U1151 - CNRS UMR 8253, Institut Necker-Enfants Malades, Equipe 11: Pathogénie des Infections Systémiques, Paris, France.
authors.forename: Jason
authors.initials: J
authors.lastname: Ziveri
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche, Paris, France.|INSERM U1151 - CNRS UMR 8253, Institut Necker-Enfants Malades, Equipe 11: Pathogénie des Infections Systémiques, Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Ramond
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche, Paris, France.|INSERM U1151 - CNRS UMR 8253, Institut Necker-Enfants Malades, Equipe 11: Pathogénie des Infections Systémiques, Paris, France.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Tros
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche, Paris, France.|INSERM U1151 - CNRS UMR 8253, Institut Necker-Enfants Malades, Equipe 11: Pathogénie des Infections Systémiques, Paris, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kock
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche, Paris, France.|INSERM U1151 - CNRS UMR 8253, Institut Necker-Enfants Malades, Equipe 11: Pathogénie des Infections Systémiques, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Dupuis
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche, Paris, France.|INSERM U1151 - CNRS UMR 8253, Institut Necker-Enfants Malades, Equipe 11: Pathogénie des Infections Systémiques, Paris, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Brillet
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche, Paris, France.|INSERM U1151 - CNRS UMR 8253, Institut Necker-Enfants Malades, Equipe 11: Pathogénie des Infections Systémiques, Paris, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Barel
authors.affiliation: Université de Toulouse, INSA, UPS, INP, LISBP, 135 Avenue de Rangueil, Toulouse, 31077, France.|INRA, UMR792, Ingénierie des Systèmes Biologiques et des Procédés, Toulouse, 31400, France.|CNRS, UMR5504, Toulouse, 31400, France.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Peyriga
authors.affiliation: Université de Toulouse, INSA, UPS, INP, LISBP, 135 Avenue de Rangueil, Toulouse, 31077, France.|INRA, UMR792, Ingénierie des Systèmes Biologiques et des Procédés, Toulouse, 31400, France.|CNRS, UMR5504, Toulouse, 31400, France.
authors.forename: Edern
authors.initials: E
authors.lastname: Cahoreau
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche, Paris, France.|INSERM U1151 - CNRS UMR 8253, Institut Necker-Enfants Malades, Equipe 11: Pathogénie des Infections Systémiques, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Charbit
mesh_terms: D000818:Animals; D005260:Female; D005604:Francisella tularensis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D005798:Genes, Bacterial; D005943:Gluconeogenesis; D056945:Hep G2 Cells; D006801:Humans; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways; D051379:Mice; D008807:Mice, Inbred BALB C; D014406:Tularemia / Q000382:microbiology; D014774:Virulence