Importance of host cell arginine uptake in Francisella phagosomal escape and ribosomal protein amounts
Résumé
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).
Mots clés
Animals
Arginine
Autophagy
Bacterial Proteins
Bacterial Vaccines
Cluster Analysis
Cytosol
Female
Francisella
Host-Pathogen Interactions
Macrophages
Membrane Transport Proteins
Mice
Inbred BALB C
Microbial Viability
Models
Biological
Mutation
Phagosomes
Protein Transport
Proteome
Ribosomal Proteins
Stress
Physiological
Subcellular Fractions
Virulence