Importance of host cell arginine uptake in Francisella phagosomal escape and ribosomal protein amounts.

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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).", "claims": [{"id": "claim-target-result", "statement": "The paper identifies ArgP as an arginine transporter whose inactivation delays phagosomal escape and intracellular multiplication; no statistical method is specified, and the source data are deposited in ProteomeXchange under PXD001584.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:25616868", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We identified and functionally characterized an arginine transporter (hereafter designated ArgP) whose inactivation considerably delayed bacterial phagosomal escape and intracellular multiplication."}, {"asset": "source:pmid:25616868", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "All MS data have been deposited in the ProteomeXchange database with identifier PXD001584 (http://proteomecentral.proteomexchange.org/dataset/PXD001584)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The paper identifies ArgP as an arginine transporter whose inactivation delays phagosomal escape and intracellular multiplication; no statistical method is specified, and the source data are deposited in ProteomeXchange under PXD001584.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:25616868"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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