ArticleEMBO molecular medicine2015
Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion.
Article in EMBO molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
103 citing papers in PubMed, 154 citations in OpenAlex.
- HowVaccines · 2026Review
- Autophagy in tuberculosis: advances, translational gaps, and the promise of host-directed therapies.Frontiers in cellular and infection microbiology · 2026Review
- Deciphering macrophage dynamics and immune evasion strategies by the intracellular bacteria.Immunologic research · 2025Review
- Host-directed therapeutic targets in macrophages and their ligands against mycobacteria tuberculosis.Infection and immunity · 2025Review
- Phagosomal RNA sensing through TLR8 controls susceptibility to tuberculosis.Cell reports · 2025Article
- Inositol Phosphates and Synthesizing Enzymes: Implications in Neurodegenerative Disorders.Biomolecules · 2025Review
- The potential of dibenzazepine carboxamides in cancer therapy.Frontiers in pharmacology · 2025Review
- Modulating autophagy in KRAS mutant colorectal cancer using combination of oncolytic reovirus and carbamazepine.PloS one · 2025Article
- Autophagy in mycobacterial infections: molecular mechanisms, host-pathogen interactions, and therapeutic opportunities.Frontiers in cellular and infection microbiology · 2025Review
- Niraparib perturbs autophagosome-lysosome fusion in pancreatic ductal adenocarcinoma and exhibits anticancer potential against gemcitabine-resistant PDAC.Translational oncology · 2025Article
- Repurposed Drugs and Plant-Derived Natural Products as Potential Host-Directed Therapeutic Candidates for Tuberculosis.Biomolecules · 2024Review
- The Role of mTOR inBiomedicines · 2024Review
- Recognition of Mycobacterium tuberculosis by macrophage Toll-like receptor and its role in autophagy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Impact of carbamazepine on SMARCA4 (BRG1) expression in colorectal cancer: modulation by KRAS mutation status.Investigational new drugs · 2024Article
- The protective effect of carbamazepine on acute lung injury induced by hemorrhagic shock and resuscitation in rats.PloS one · 2024Article
- The engagement of autophagy in maniac disease.CNS neuroscience & therapeutics · 2023Review
- Review
- Valproate regulates inositol synthesis by reducing expression of myo-inositol-3-phosphate synthase.Scientific reports · 2023Article
- Identification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro.Pharmaceutics · 2023Article
- The crosslinks between ferroptosis and autophagy in asthma.Frontiers in immunology · 2023Review
43 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
22 authors at 7 institutions in 2 countries.
Funding
Abstract
Mycobacterium tuberculosis (MTB) remains a major challenge to global health made worse by the spread of multidrug resistance. We therefore examined whether stimulating intracellular killing of mycobacteria through pharmacological enhancement of macroautophagy might provide a novel therapeutic strategy. Despite the resistance of MTB to killing by basal autophagy, cell-based screening of FDA-approved drugs revealed two anticonvulsants, carbamazepine and valproic acid, that were able to stimulate autophagic killing of intracellular M. tuberculosis within primary human macrophages at concentrations achievable in humans. Using a zebrafish model, we show that carbamazepine can stimulate autophagy in vivo and enhance clearance of M. marinum, while in mice infected with a highly virulent multidrug-resistant MTB strain, carbamazepine treatment reduced bacterial burden, improved lung pathology and stimulated adaptive immunity. We show that carbamazepine induces antimicrobial autophagy through a novel, evolutionarily conserved, mTOR-independent pathway controlled by cellular depletion of myo-inositol. While strain-specific differences in susceptibility to in vivo carbamazepine treatment may exist, autophagy enhancement by repurposed drugs provides an easily implementable potential therapy for the treatment of multidrug-resistant mycobacterial infection.
Indexed as
Identifiers
What OpenQuestion holds
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.