title: Importance of host cell arginine uptake in Francisella phagosomal escape and ribosomal protein amounts.
abstract: Upon entry into mammalian host cells, the pathogenic bacterium Francisella must import host cell arginine to multiply actively in the host cytoplasm. We identified and functionally characterized an arginine transporter (hereafter designated ArgP) whose inactivation considerably delayed bacterial phagosomal escape and intracellular multiplication. Intramacrophagic growth of the ΔargP mutant was fully restored upon supplementation of the growth medium with excess arginine, in both F. tularensis subsp. novicida and F. tularensis subsp. holarctica LVS, demonstrating the importance of arginine acquisition in these two subspecies. High-resolution mass spectrometry revealed that arginine limitation reduced the amount of most of the ribosomal proteins in the ΔargP mutant. In response to stresses such as nutritional limitation, repression of ribosomal protein synthesis has been observed in all kingdoms of life. Arginine availability may thus contribute to the sensing of the intracellular stage of the pathogen and to trigger phagosomal egress. All MS data have been deposited in the ProteomeXchange database with identifier PXD001584 (http://proteomecentral.proteomexchange.org/dataset/PXD001584).
authors.affiliation: From the ‡Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche; §INSERM U1151-CNRS UMR 8253, Institut Necker-Enfants Malades, Team 11. Paris, France;
authors.forename: Elodie
authors.initials: E
authors.lastname: Ramond
authors.affiliation: From the ‡Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche; §INSERM U1151-CNRS UMR 8253, Institut Necker-Enfants Malades, Team 11. Paris, France;
authors.forename: Gael
authors.initials: G
authors.lastname: Gesbert
authors.affiliation: From the ‡Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche; ¶Plateforme Protéome Institut Necker, PPN, Structure Fédérative de Recherche SFR Necker, Université Paris Descartes, Paris 75015 France;
authors.forename: Ida Chiara
authors.initials: IC
authors.lastname: Guerrera
authors.affiliation: From the ‡Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche; ¶Plateforme Protéome Institut Necker, PPN, Structure Fédérative de Recherche SFR Necker, Université Paris Descartes, Paris 75015 France;
authors.forename: Cerina
authors.initials: C
authors.lastname: Chhuon
authors.affiliation: From the ‡Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche; §INSERM U1151-CNRS UMR 8253, Institut Necker-Enfants Malades, Team 11. Paris, France;
authors.forename: Marion
authors.initials: M
authors.lastname: Dupuis
authors.affiliation: ‖CIRI, Centre International de Recherche en Infectiologie, Lyon, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Rigard
authors.affiliation: ‖CIRI, Centre International de Recherche en Infectiologie, Lyon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Henry
authors.affiliation: From the ‡Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche; §INSERM U1151-CNRS UMR 8253, Institut Necker-Enfants Malades, Team 11. Paris, France;
authors.forename: Monique
authors.initials: M
authors.lastname: Barel
authors.affiliation: From the ‡Université Paris Descartes, Sorbonne Paris Cité, Bâtiment Leriche; §INSERM U1151-CNRS UMR 8253, Institut Necker-Enfants Malades, Team 11. Paris, France; alain.charbit@inserm.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Charbit
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D001343:Autophagy; D001426:Bacterial Proteins / Q000378:metabolism; D001428:Bacterial Vaccines / Q000276:immunology; D016000:Cluster Analysis; D003600:Cytosol / Q000378:metabolism; D005260:Female; D005603:Francisella / Q000378:metabolism* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D026901:Membrane Transport Proteins / Q000378:metabolism; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D010588:Phagosomes / Q000378:metabolism / Q000382:microbiology* / Q000648:ultrastructure; D021381:Protein Transport; D020543:Proteome / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism*; D013312:Stress, Physiological; D013347:Subcellular Fractions / Q000378:metabolism; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D026901:Membrane Transport Proteins; D020543:Proteome; D012269:Ribosomal Proteins; D001120:Arginine