ArticleInfection and immunity2003
Inhibition of Mycobacterium tuberculosis glutamine synthetase as a novel antibiotic strategy against tuberculosis: demonstration of efficacy in vivo.
Article in Infection and immunity, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 83 citations in OpenAlex.
- Protection Elicited by Glutamine Auxotroph ofVaccines · 2025Article
- Glutamine Synthetase: Diverse Regulation and Functions of an Ancient Enzyme.Biochemistry · 2025Review
- Where lung cancer and tuberculosis intersect: recent advances.Frontiers in immunology · 2025Review
- Model systems to studyFrontiers in cellular and infection microbiology · 2025Review
- Glutamine metabolism inhibition has dual immunomodulatory and antibacterial activities against Mycobacterium tuberculosis.Nature communications · 2023Article
- Nitrogen metabolism in mycobacteria: the key genes and targeted antimicrobials.Frontiers in microbiology · 2023Review
- Novel Potential Diagnostic Serum Biomarkers of Metabolomics in Osteoarticular Tuberculosis Patients: A Preliminary Study.Frontiers in cellular and infection microbiology · 2022Article
- Identification of Concomitant Inhibitors against Glutamine Synthetase and Isocitrate Lyase inBioMed research international · 2022Article
- Assembly status transition offers an avenue for activity modulation of a supramolecular enzyme.eLife · 2021Article
- Active and prospective latent tuberculosis are associated with different metabolomic profiles: clinical potential for the identification of rapid and non-invasive biomarkers.Emerging microbes & infections · 2020Article
- Potential therapeutic approaches for a sleeping pathogen: tuberculosis a case for bioinorganic chemistry.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020Review
- Inactivation of Glutamine Synthetase-Coding GeneFrontiers in microbiology · 2020Article
- Intracellular Mycobacterium tuberculosis Exploits Multiple Host Nitrogen Sources during Growth in Human Macrophages.Cell reports · 2019Article
- Mode-of-action profiling reveals glutamine synthetase as a collateral metabolic vulnerability ofProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Synthesis, In Vitro Screening and Docking Studies of New Thiosemicarbazide Derivatives as Antitubercular Agents.Molecules (Basel, Switzerland) · 2019Article
- Arsinothricin, an arsenic-containing non-proteinogenic amino acid analog of glutamate, is a broad-spectrum antibiotic.Communications biology · 2019Article
- Mechanistic Basis for ATP-Dependent Inhibition of Glutamine Synthetase by Tabtoxinine-β-lactam.Biochemistry · 2018Article
- Review
- Differential inhibition of adenylylated and deadenylylated forms of M. tuberculosis glutamine synthetase as a drug discovery platform.PloS one · 2017Article
- Glutamine Synthetase Drugability beyond Its Active Site: Exploring Oligomerization Interfaces and Pockets.Molecules (Basel, Switzerland) · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Tuberculosis remains one of humankind's greatest killers, and new therapeutic strategies are needed to combat the causative agent, Mycobacterium tuberculosis, which is rapidly developing resistance to conventional antibiotics. Using the highly demanding guinea pig model of pulmonary tuberculosis, we have investigated the feasibility of inhibiting M. tuberculosis glutamine synthetase (GS), an enzyme that plays a key role in both nitrogen metabolism and cell wall biosynthesis, as a novel antibiotic strategy. In guinea pigs challenged by aerosol with the highly virulent Erdman strain of M. tuberculosis, the GS inhibitor L-methionine-SR-sulfoximine (MSO) protected the animals against weight loss, a hallmark of tuberculosis, and against the growth of M. tuberculosis in the lungs and spleen; MSO reduced the CFU of M. tuberculosis at 10 weeks after challenge by approximately 0.7 log unit compared with that in control animals. MSO acted synergistically with isoniazid in protecting animals against weight loss and bacterial growth, reducing the CFU in the lungs and spleen by approximately 1.5 log units below the level seen with isoniazid alone. In the presence of ascorbate, which allows treatment with a higher dose, MSO was highly efficacious, reducing the CFU in the lungs and spleen by 2.5 log units compared with that in control animals. This study demonstrates that inhibition of M. tuberculosis GS is a feasible therapeutic strategy against this pathogen and supports the concept that M. tuberculosis enzymes involved in cell wall biosynthesis, including major secretory proteins, have potential as antibiotic targets.
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Registered trials
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.