Importance of Host Cell Arginine Uptake in Francisella Phagosomal Escape and Ribosomal Protein Amounts[S]

• Published in: Molecular & cellular proteomics Vol. 14; no. 4; pp. 870 - 881
• Main Authors: Ramond, Elodie, Gesbert, Gael, Guerrera, Ida Chiara, Chhuon, Cerina, Dupuis, Marion, Rigard, Mélanie, Henry, Thomas, Barel, Monique, Charbit, Alain
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2015; American Society for Biochemistry and Molecular Biology; The American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Arginine - metabolism; Autophagy; Bacterial Proteins - metabolism; Bacterial Vaccines - immunology; Bacteriology; Cluster Analysis; Cytosol - metabolism; Female; Francisella; Francisella - metabolism; Francisella - pathogenicity; Host-Pathogen Interactions; Immunology; Life Sciences; Macrophages - metabolism; Macrophages - microbiology; Macrophages - ultrastructure; Membrane Transport Proteins - metabolism; Mice, Inbred BALB C; Microbial Viability; Microbiology and Parasitology; Models, Biological; Mutation - genetics; Phagosomes - metabolism; Phagosomes - microbiology; Phagosomes - ultrastructure; Protein Transport; Proteome - metabolism; Ribosomal Proteins - metabolism; Stress, Physiological; Subcellular Fractions - metabolism; Virology; Virulence; Inbred BALB C; Virulence; Phagosomes; Macrophages; Autophagy; Cytosol; Arginine; Francisella; Female; Proteome; Microbial Viability; Biological; Bacterial Vaccines; Stress; Bacterial Proteins; Protein Transport; Host-Pathogen Interactions; Animals; Membrane Transport Proteins; Mice; Models; Mutation; Subcellular Fractions; Physiological; Cluster Analysis; Ribosomal Proteins
• ISSN: 1535-9476; 1535-9484
• DOI: 10.1074/mcp.M114.044552

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).