ArticleAntimicrobial agents and chemotherapy2013
Gallium nitrate is efficacious in murine models of tuberculosis and inhibits key bacterial Fe-dependent enzymes.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 66 citations in OpenAlex.
- Repurposing the Anticancer Drug KP46 to Beat the CRAB out of Resistance: Towards an Orally Active Ga-Based Antiplantonic and Antibiofilm Agent.Antibiotics (Basel, Switzerland) · 2025Article
- How macrophage heterogeneity affects tuberculosis disease and therapy.Nature reviews. Immunology · 2025Review
- Bactericidal Metal-Organic Gallium Frameworks - Synthesis to Application.Molecular pharmaceutics · 2025Review
- Escherichia coli growing under antimicrobial gallium nitrate stress reveals new processes of tolerance and toxicity.Scientific reports · 2025Article
- Efficacy and Possible Mechanism(s) of Action of Gallium Tetraphenylporphyrin Nanoparticles against HIV-TB Coinfection in anACS infectious diseases · 2024Article
- Quantitative proteomic analysis reveals Ga(III) polypyridyl catecholate complexes disrupt Aspergillus fumigatus mitochondrial function.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2024Article
- Antimicrobial Activity of Gallium(III) Compounds: Pathogen-Dependent Targeting of Multiple Iron/Heme-Dependent Biological Processes.Current issues in molecular biology · 2024Review
- Integrating bacterial molecular genetics with chemical biology for renewed antibacterial drug discovery.The Biochemical journal · 2024Review
- In Silico Analysis of the GaBiomolecules · 2024Article
- pH-mediated potentiation of gallium nitrate againstFrontiers in microbiology · 2024Article
- Combination of gallium citrate and levofloxacin induces a distinct metabolome profile and enhances growth inhibition of multidrug-resistantFrontiers in microbiology · 2024Article
- Synthesis of Antimicrobial Gallium Nanoparticles Using the Hot Injection Method.ACS materials Au · 2023Article
- An Insight into Advances in Developing Nanotechnology Based Therapeutics, Drug Delivery, Diagnostics and Vaccines: Multidimensional Applications in Tuberculosis Disease Management.Pharmaceuticals (Basel, Switzerland) · 2023Review
- A Review of the Development of Multitarget Molecules against HIV-TB Coinfection Pathogens.Molecules (Basel, Switzerland) · 2023Review
- Gallium-Based Liquid Metal Materials for Antimicrobial Applications.Bioengineering (Basel, Switzerland) · 2022Review
- Iron limitation in M. tuberculosis has broad impact on central carbon metabolism.Communications biology · 2022Article
- Gain-of-Function Mutations in Acid Stress Response (Antimicrobial agents and chemotherapy · 2021Article
- Quantitative proteomic reveals gallium maltolate induces an iron-limited stress response and reduced quorum-sensing in Pseudomonas aeruginosa.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020Article
- Dual RNA-Seq of Mtb-Infected Macrophages In Vivo Reveals Ontologically Distinct Host-Pathogen Interactions.Cell reports · 2020Article
- Children With Cystic Fibrosis Are Infected With Multiple Subpopulations of Mycobacterium abscessus With Different Antimicrobial Resistance Profiles.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Article
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acquiring iron (Fe) is critical to the metabolism and growth of Mycobacterium tuberculosis. Disruption of Fe metabolism is a potential approach for novel antituberculous therapy. Gallium (Ga) has many similarities to Fe. Biological systems are often unable to distinguish Ga(3+) from Fe(3+). Unlike Fe(3+), Ga(3+) cannot be physiologically reduced to Ga(2+). Thus, substituting Ga for Fe in the active site of enzymes may render them nonfunctional. We previously showed that Ga inhibits growth of M. tuberculosis in broth and within cultured human macrophages. We now report that Ga(NO3)3 shows efficacy in murine tuberculosis models. BALB/c SCID mice were infected intratracheally with M. tuberculosis, following which they received daily intraperitoneal saline, Ga(NO3)3, or NaNO3. All mice receiving saline or NaNO3 died. All Ga(NO3)3-treated mice survived. M. tuberculosis CFU in the lungs, liver, and spleen of the NaNO3-treated or saline-treated mice were significantly higher than those in Ga-treated mice. When BALB/c mice were substituted for BALB/c SCID mice as a chronic (nonlethal) infection model, Ga(NO3)3 treatment significantly decreased lung CFU. To assess the mechanism(s) whereby Ga inhibits bacterial growth, the effect of Ga on M. tuberculosis ribonucleotide reductase (RR) (a key enzyme in DNA replication) and aconitase activities was assessed. Ga decreased M. tuberculosis RR activity by 50 to 60%, but no additional decrease in RR activity was seen at Ga concentrations that completely inhibited mycobacterial growth. Ga decreased aconitase activity by 90%. Ga(NO3)3 shows efficacy in murine M. tuberculosis infection and leads to a decrease in activity of Fe-dependent enzymes. Additional work is warranted to further define Ga's mechanism of action and to optimize delivery forms for possible therapeutic uses in humans.
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