{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Schiebler M"],"funding":["Medical Research Council","Wellcome Trust","Biotechnology and Biological Sciences Research Council"],"pagination":["127-39"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4328644"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(2)"],"pubmed_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"],"journal":["EMBO molecular medicine"],"pubmed_title":["Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion."],"pmcid":["PMC4328644"],"funding_grant_id":["100140","MC_U105115237","MR/M004864/1","095317","G108/595","G0701932","BBS/E/B/000C0415"],"pubmed_authors":["Renna M","Basaraba R","Rubinsztein DC","Henao Tamayo M","Anderson KE","Obregon-Henao A","Ordway DJ","Hawkins PT","Newton SM","Renshaw SA","Coulter S","Fleming A","Kay RR","Brown K","Henry KM","Kampmann B","Floto RA","Hegyi K","Klapholz C","Hepburn L","Schiebler M","Burgon J"],"additional_accession":[]},"is_claimable":false,"name":"Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion.","description":"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","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Feb","modification":"2025-04-04T10:01:39.149Z","creation":"2019-03-27T01:45:13Z"},"accession":"S-EPMC4328644","cross_references":{"pubmed":["25535254"],"doi":["10.15252/emmm.201404137"]}}