ArticleAntimicrobial agents and chemotherapy2012
Evaluation of a mouse model of necrotic granuloma formation using C3HeB/FeJ mice for testing of drugs against Mycobacterium tuberculosis.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers, 1 of them a synthesis that pooled it.
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Who cites it
175 citing papers in PubMed, 1 synthesis or guideline pooled it, 271 citations in OpenAlex.
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- Monocytic niches escape T cell surveillance and promote Mycobacterium tuberculosis persistence in lymph nodes.Immunity · 2026Article
- Fast-growing intracellular Mycobacterium tuberculosis populations evade antibiotic treatment.Nature communications · 2026Article
- Infection dose shapes granuloma phenotypes in a humanized mouse model of tuberculosis.Research square · 2026Article
- Lipid accumulation in tuberculosis granulomas inhibits macrophage-CD4Nature microbiology · 2026Article
- The immunometabolic topography of cellular organization and bacterial control in tuberculosis granulomas.Nature immunology · 2026Article
- Strain-dependent disease progression and necrotizing granuloma formation in a murine model induced by virulent strains ofMicrobiology spectrum · 2026Article
- Mouse models of tuberculosis uniformly featuring hypoxic necrotic lesions and poor response to chemotherapy.Infection and immunity · 2026Article
- Post-TB lung disease: pathogenesis, host-directed therapies, and the C3HeB/FeJ model for pre-clinical advances.Infection and immunity · 2026Review
- Essential role of MHC II in the antitubercular efficacy of pyrazinamide.Antimicrobial agents and chemotherapy · 2026Article
- Repeated pulmonary dosing of β-glucan-chitosan-PLGA nanoparticles controlsAntimicrobial agents and chemotherapy · 2026Article
- PET/CT imaging of tuberculosis lung lesions in marmosets treated with different drug regimens aligns with human clinical outcomes.Science translational medicine · 2026Article
- Article
- Spatial and temporal immune landscapes of non-necrotic granulomas in two murine tuberculosis models with divergent disease outcomes.Frontiers in immunology · 2026Article
- The eight pillars of within-host tuberculosis modelling.Frontiers in immunology · 2026Review
- Tissue-specific untargetedFrontiers in pharmacology · 2026Article
- Inflammatory Macrophages Associate With Tissue Injury and Fibrosis in a Mouse Model of Tuberculosis.The Journal of infectious diseases · 2025Article
- Mycobacterium tuberculosis biology, pathogenicity and interaction with the host.Nature reviews. Microbiology · 2025Review
115 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Persistence of Mycobacterium tuberculosis remains a significant challenge for the effective treatment of tuberculosis in humans. In animals that develop necrotic lung lesions following infection with M. tuberculosis, drug-tolerant bacilli are present and persist in an extracellular microenvironment within the necrotic cores. In this study, we examined the efficacy of drug treatment in C3HeB/FeJ (Kramnik) mice that develop lesions with liquefactive necrosis, in comparison to BALB/c mice that develop nonnecrotic lesions following aerosol challenge. To accomplish this, Kramnik and BALB/c mice were infected by aerosol with M. tuberculosis and treated for 7 to 8 weeks with monotherapy using drugs with different modes of action. The efficacy of drug therapy was quantified by enumeration of bacterial load. The progression of disease and location and distribution of bacilli within lesions were visualized using various staining techniques. In the late stages of infection, Kramnik mice developed fibrous encapsulated lung lesions with central liquefactive necrosis containing abundant extracellular bacilli, whereas BALB/c mice formed nonnecrotic lesions with primarily intracellular bacilli. Necrotic lesions in Kramnik mice showed evidence of hypoxia by pimonidazole staining. Kramnik mice were significantly more refractory to drug therapy, especially for pyrazinamide. Metronidazole showed no bactericidal activity in either model. There were significantly higher numbers of drug-resistant colonies isolated from the Kramnik mice compared to BALB/c mice. These results suggest that the Kramnik mouse model will be a valuable model to test antituberculosis drugs, especially against bacilli that persist within necrotic lesions.
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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.