ArticlePLoS pathogens2020
Potentiation of rifampin activity in a mouse model of tuberculosis by activation of host transcription factor EB.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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
13 citing papers in PubMed, 17 citations in OpenAlex.
- Exploiting autophagy-targeting natural compounds for potential antimicrobial actions.Autophagy · 2026Review
- Bioinformatics and experimental analysis identify CHN2 and MEF2C as diagnostic biomarkers for tuberculosis.American journal of translational research · 2026Article
- Overcoming Treatment Challenges in HIV-Associated Mycobacterial Diseases: New Therapeutic Frontiers.International journal of molecular sciences · 2025Review
- Unraveling Mycobacterium tuberculosis acid resistance and pH homeostasis mechanisms.FEBS letters · 2025Review
- ACOD1-mediated lysosomal membrane permeabilization contributes toProceedings of the National Academy of Sciences of the United States of America · 2025Article
- High throughput screening assay for the identification of ATF4 and TFEB activating compounds.Autophagy reports · 2025Article
- Autophagy in mycobacterial infections: molecular mechanisms, host-pathogen interactions, and therapeutic opportunities.Frontiers in cellular and infection microbiology · 2025Review
- Mycobacterium tuberculosis resides in lysosome-poor monocyte-derived lung cells during chronic infection.PLoS pathogens · 2024Article
- Interferon-Science (New York, N.Y.) · 2024Review
- Differential Regulation of TFEB-Induced Autophagy during Mtb Infection and Starvation.Microorganisms · 2023Review
- A guide to membrane atg8ylation and autophagy with reflections on immunity.The Journal of cell biology · 2022Article
- Intracellular localisation of Mycobacterium tuberculosis affects efficacy of the antibiotic pyrazinamide.Nature communications · 2021Article
- Host-directed therapy to combat mycobacterial infections.Immunological reviews · 2021Review
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 3 countries.
Funding
Abstract
Efforts at host-directed therapy of tuberculosis have produced little control of the disease in experimental animals to date. This is not surprising, given that few specific host targets have been validated, and reciprocally, many of the compounds tested potentially impact multiple targets with both beneficial and detrimental consequences. This puts a premium on identifying appropriate molecular targets and subjecting them to more selective modulation. We discovered an aminopyrimidine small molecule, 2062, that had no direct antimycobacterial activity, but synergized with rifampin to reduce bacterial burden in Mtb infected macrophages and mice and also dampened lung immunopathology. We used 2062 and its inactive congeners as tool compounds to identify host targets. By biochemical, pharmacologic, transcriptomic and genetic approaches, we found that 2062's beneficial effects on Mtb control and clearance in macrophages and in mice are associated with activation of transcription factor EB via an organellar stress response. 2062-dependent TFEB activation led to improved autophagy, lysosomal acidification and lysosomal degradation, promoting bacterial clearance in macrophages. Deletion of TFEB resulted in the loss of IFNγ-dependent control of Mtb replication in macrophages. 2062 also targeted multiple kinases, such as PIKfyve, VPS34, JAKs and Tyk2, whose inhibition likely limited 2062's efficacy in vivo. These findings support a search for selective activators of TFEB for HDT of TB.
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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.