ArticleNature communications2023
Glutamine metabolism inhibition has dual immunomodulatory and antibacterial activities against Mycobacterium tuberculosis.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 31 citations in OpenAlex.
- The Kynurenine Pathway in Tuberculosis: Focus on Immunometabolic Regulation, Compartment-Specific Biology, and Therapeutic Potential.Life (Basel, Switzerland) · 2026Review
- Zinc displacement and metabolic interference: cobalt ion-mediated therapy for broad-spectrum CRKP-resistant pneumonia via inhalable microspheres.Nature communications · 2026Article
- Synergistic eradication of NDM-1Materials today. Bio · 2026Article
- Pathogenesis of Tuberculosis: Interplay Between Host Antituberculosis Immunity and Immune Evasion Strategies ofMedComm · 2026Review
- Mycobacterium tuberculosis preferentially infects specific macrophage subsets in primate granulomas during the early stages of tuberculosis.Mucosal immunology · 2026Article
- Safety, Tolerability, and Pharmacokinetics of 6-Diazo-5-Oxo-L-Norleucine in Malawian Adults With and Without Malaria: A Phase 1 Dose-Escalation Clinical Trial.The Journal of infectious diseases · 2026Article
- Single-cell RNA sequencing reveals that host Glutamine Metabolism Inhibition Enhances Macrophage Phagocytosis ofbioRxiv : the preprint server for biology · 2026Article
- Elimination of senescent cells with senolytic drugs as adjunctive host-directed therapy reduces tuberculosis progression in mice.Nature communications · 2026Article
- Metabolites from plasma-like medium fuel nitrogen metabolism and influence proliferation inbioRxiv : the preprint server for biology · 2026Article
- Androgen Receptor Drives Polyamine Synthesis, Creating a Vulnerability for Prostate Cancer.Cancer research · 2026Article
- Multi-Targeted Therapeutic Mechanisms of Huangqi Guizhi Wuwu Decoction Against Rheumatoid Arthritis: An Integrated Approach Combining Serum Pharmacochemistry, Network Pharmacology, Metabolomics, and Experimental Validation.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Metabolic reprogramming of macrophages during mycobacterial infection: a review of immunometabolic crosstalk and pathogen manipulation.Frontiers in cellular and infection microbiology · 2026Review
- A Key Metabolic Protein in Active Mycobacterium tuberculosis: Insights into Carbon, Nitrogen, and Sulfur Metabolism.Advances in experimental medicine and biology · 2026Review
- Intracellular pH links energy metabolism to lymphocyte death and proliferation.Scientific reports · 2025Article
- Oral oncolytic magnetotactic bacteria elicit anti-colorectal tumor immunity and reprogram microbiota metabolism.Bioactive materials · 2025Article
- Natural Killer Cell-Mediated Antitumor Immunity: Molecular Mechanisms and Clinical Applications.MedComm · 2025Review
- Glutaminase inhibition ameliorates cancer-associated fibroblast lipid support of pancreatic cancer cell growth.Cancer & metabolism · 2025Article
- Metabolic Changes in Zebrafish Larvae Infected withMetabolites · 2025Article
- Host-directed therapy for tuberculosis.European journal of medical research · 2025Review
- Glutamine Synthetase: Diverse Regulation and Functions of an Ancient Enzyme.Biochemistry · 2025Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
As one of the most successful human pathogens, Mycobacterium tuberculosis (Mtb) has evolved a diverse array of determinants to subvert host immunity and alter host metabolic patterns. However, the mechanisms of pathogen interference with host metabolism remain poorly understood. Here we show that a glutamine metabolism antagonist, JHU083, inhibits Mtb proliferation in vitro and in vivo. JHU083-treated mice exhibit weight gain, improved survival, a 2.5 log lower lung bacillary burden at 35 days post-infection, and reduced lung pathology. JHU083 treatment also initiates earlier T-cell recruitment, increased proinflammatory myeloid cell infiltration, and a reduced frequency of immunosuppressive myeloid cells when compared to uninfected and rifampin-treated controls. Metabolomic analysis of lungs from JHU083-treated Mtb-infected mice reveals citrulline accumulation, suggesting elevated nitric oxide (NO) synthesis, and lowered levels of quinolinic acid which is derived from the immunosuppressive metabolite kynurenine. JHU083-treated macrophages also produce more NO potentiating their antibacterial activity. When tested in an immunocompromised mouse model of Mtb infection, JHU083 loses its therapeutic efficacy suggesting the drug's host-directed effects are likely to be predominant. Collectively, these data reveal that JHU083-mediated glutamine metabolism inhibition results in dual antibacterial and host-directed activity against tuberculosis.
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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.