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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\u2010based screening of FDA\u2010approved drugs revealed two anticonvulsants, carbamazepine and valproic acid, that were able to stimulate autophagic killing of intracellular\n                    <jats:italic>M.\u00a0tuberculosis<\/jats:italic>\n                    within primary human macrophages at concentrations achievable in humans. Using a zebrafish model, we show that carbamazepine can stimulate autophagy\n                    <jats:italic>in vivo<\/jats:italic>\n                    and enhance clearance of\n                    <jats:italic>M.\u00a0marinum<\/jats:italic>\n                    , while in mice infected with a highly virulent multidrug\u2010resistant 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\u2010independent pathway controlled by cellular depletion of myo\u2010inositol. While strain\u2010specific differences in susceptibility to\n                    <jats:italic>in vivo<\/jats:italic>\n                    carbamazepine treatment may exist, autophagy enhancement by repurposed drugs provides an easily implementable potential therapy for the treatment of multidrug\u2010resistant mycobacterial infection.\n                  <\/jats:p>","DOI":"10.15252\/emmm.201404137","type":"journal-article","created":{"date-parts":[[2014,12,23]],"date-time":"2014-12-23T00:12:13Z","timestamp":1419293533000},"page":"127-139","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":159,"title":["Functional drug screening reveals anticonvulsants as enhancers of mTOR\u2010independent autophagic killing of Mycobacterium tuberculosis through inositol depletion"],"prefix":"10.1038","volume":"7","author":[{"given":"Mark","family":"Schiebler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisztina","family":"Hegyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra M","family":"Newton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Renna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Hepburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Klapholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Coulter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Obreg\u00f3n\u2010Henao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Henao Tamayo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall","family":"Basaraba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Kampmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine M","family":"Henry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Burgon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A","family":"Renshaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeleen","family":"Fleming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R","family":"Kay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen E","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip T","family":"Hawkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane J","family":"Ordway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C","family":"Rubinsztein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Andres","family":"Floto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,12,22]]},"reference":[{"key":"BFEMMM201404137_CR1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1128\/MCB.06159-11","volume":"32","author":"S Alers","year":"2011","unstructured":"Alers S, L\u00f6ffler AS, Wesselborg S, Stork B (2011) Role of AMPK\u2010mTOR\u2010Ulk1\/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. 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