ArticleInfection and immunity2015
Importance of branched-chain amino acid utilization in Francisella intracellular adaptation.
Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Adaptive metabolic strategies of intracellular bacterial pathogens.Frontiers in microbiology · 2026Review
- Review
- Diverse roles of low-molecular weight thiol GSH inCurrent research in microbial sciences · 2024Article
- Pathogenicity and virulence ofVirulence · 2023Review
- Common pathogenic bacteria-induced reprogramming of the host proteinogenic amino acids metabolism.Amino acids · 2023Review
- Discovery of a glutathione utilization pathway in Francisella that shows functional divergence between environmental and pathogenic species.Cell host & microbe · 2023Article
- Comparative analysis of absent in melanoma 2-inflammasome activation inFrontiers in microbiology · 2023Article
- Francisella tularensis Exploits AMPK Activation to Harvest Host-Derived Nutrients Liberated from Host Lipolysis.Infection and immunity · 2022Article
- Deletion Mutants ofPathogens (Basel, Switzerland) · 2021Article
- Single amino acid utilization for bacterial categorization.Scientific reports · 2020Article
- Article
- Engineering a defined culture medium to grow Piscirickettsia salmonis for its use in vaccine formulations.Journal of industrial microbiology & biotechnology · 2020Article
- Critical Role of a Sheath Phosphorylation Site On the Assembly and Function of an Atypical Type VI Secretion System.Molecular & cellular proteomics : MCP · 2019Article
- Article
- Review
- Deletion of the Major Facilitator Superfamily TransporterInfection and immunity · 2018Article
- The metabolic enzyme fructose-1,6-bisphosphate aldolase acts as a transcriptional regulator in pathogenic Francisella.Nature communications · 2017Article
- Characterization of Brucella abortus mutant strain Δ22915, a potential vaccine candidate.Veterinary research · 2017Article
- Review
- Differential Substrate Usage and Metabolic Fluxes inFrontiers in cellular and infection microbiology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellular bacterial pathogens have adapted their metabolism to optimally utilize the nutrients available in infected host cells. We recently reported the identification of an asparagine transporter required specifically for cytosolic multiplication of Francisella. In the present work, we characterized a new member of the major super family (MSF) of transporters, involved in isoleucine uptake. We show that this transporter (here designated IleP) plays a critical role in intracellular metabolic adaptation of Francisella. Inactivation of IleP severely impaired intracellular F. tularensis subsp. novicida multiplication in all cell types tested and reduced bacterial virulence in the mouse model. To further establish the importance of the ileP gene in F. tularensis pathogenesis, we constructed a chromosomal deletion mutant of ileP (ΔFTL_1803) in the F. tularensis subsp. holarctica live vaccine strain (LVS). Inactivation of IleP in the F. tularensis LVS provoked comparable intracellular growth defects, confirming the critical role of this transporter in isoleucine uptake. The data presented establish, for the first time, the importance of isoleucine utilization for efficient phagosomal escape and cytosolic multiplication of Francisella and suggest that virulent F. tularensis subspecies have lost their branched-chain amino acid biosynthetic pathways and rely exclusively on dedicated uptake systems. This loss of function is likely to reflect an evolution toward a predominantly intracellular life style of the pathogen. Amino acid transporters should be thus considered major players in the adaptation of intracellular pathogens.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.