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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2017,3,14]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    A better understanding of essential processes in\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic>Mtb<\/jats:italic>\n                    ) is required for the development of new chemotherapeutics. Isocitrate lyase (ICL) and malate synthase (MS) function in the glyoxylate shunt, a pathway required by\n                    <jats:italic>Mtb<\/jats:italic>\n                    to metabolize fatty acids (FAs). Here, we demonstrate that\n                    <jats:italic>Mtb<\/jats:italic>\n                    MS enables growth and survival on fatty acids through its ability to simultaneously detoxify a metabolic byproduct arising from the initial assimilation of acetyl coenzyme A (acetyl-CoA), glyoxylate, while assimilating a second molecule of acetyl-CoA. We further show that MS depletion during acute and chronic mouse infections kills\n                    <jats:italic>Mtb<\/jats:italic>\n                    . These studies expand our fundamental understanding of the glyoxylate shunt and biologically validate MS as an attractive drug target in\n                    <jats:italic>Mtb<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.1617655114","type":"journal-article","created":{"date-parts":[[2017,3,6]],"date-time":"2017-03-06T21:00:34Z","timestamp":1488834034000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":100,"title":["Glyoxylate detoxification is an essential function of malate synthase required for carbon assimilation in\n                    <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1073","volume":"114","author":[{"given":"Susan","family":"Puckett","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Trujillo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY 10021;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyungjin","family":"Eoh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY 10021;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Ioerger","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Texas A&amp;M University, College Station, TX 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Krieger","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Texas A&amp;M University, College Station, TX 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Sacchettini","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Texas A&amp;M University, College Station, TX 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Schnappinger","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu Y.","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY 10021;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Ehrt","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10021;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2017,3,6]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"163","article-title":"Mycobacterium tuberculosis metabolism and host interaction: Mysteries and paradoxes","volume":"374","author":"Ehrt S","year":"2013","unstructured":"S Ehrt, K Rhee, Mycobacterium tuberculosis metabolism and host interaction: Mysteries and paradoxes. 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