{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:20:44Z","timestamp":1789593644788,"version":"build-2803163510"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T00:00:00Z","timestamp":1474588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The recent development and spread of extensively drug-resistant and totally drug-resistant resistant (TDR) strains of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium tuberculosis<\/jats:named-content>\n            highlight the need for new antitubercular drugs. Protein synthesis inhibitors have played an important role in the treatment of tuberculosis (TB) starting with the inclusion of streptomycin in the first combination therapies. Although parenteral aminoglycosides are a key component of therapy for multidrug-resistant TB, the oxazolidinone linezolid is the only orally available protein synthesis inhibitor that is effective against TB. Here, we show that small-molecule inhibitors of aminoacyl-tRNA synthetases (AARSs), which are known to be excellent antibacterial protein synthesis targets, are orally bioavailable and effective against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            in TB mouse infection models. We applied the oxaborole tRNA-trapping (OBORT) mechanism, which was first developed to target fungal cytoplasmic leucyl-tRNA synthetase (LeuRS), to\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            LeuRS. X-ray crystallography was used to guide the design of LeuRS inhibitors that have good biochemical potency and excellent whole-cell activity against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n            . Importantly, their good oral bioavailability translates into\n            <jats:italic>in vivo<\/jats:italic>\n            efficacy in both the acute and chronic mouse models of TB with potency comparable to that of the frontline drug isoniazid.\n          <\/jats:p>","DOI":"10.1128\/aac.01339-16","type":"journal-article","created":{"date-parts":[[2016,8,9]],"date-time":"2016-08-09T02:53:53Z","timestamp":1470711233000},"page":"6271-6280","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":118,"title":["Discovery of Novel Oral Protein Synthesis Inhibitors of Mycobacterium tuberculosis That Target Leucyl-tRNA Synthetase"],"prefix":"10.1128","volume":"60","author":[{"given":"Andr\u00e9s","family":"Palencia","sequence":"first","affiliation":[{"name":"European Molecular Biology Laboratory, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Bu","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai","family":"Choi","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles Z.","family":"Ding","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric E.","family":"Easom","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Feng","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Houston","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Liu","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maliwan","family":"Meewan","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Mohan","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando L.","family":"Rock","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Sexton","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suoming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasheen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baojie","family":"Wan","sequence":"additional","affiliation":[{"name":"Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehong","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott G.","family":"Franzblau","sequence":"additional","affiliation":[{"name":"Institute for Tuberculosis Research, University of Illinois at Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Woolhiser","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Gruppo","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne J.","family":"Lenaerts","sequence":"additional","affiliation":[{"name":"Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"O'Malley","sequence":"additional","affiliation":[{"name":"TB Discovery Research, Infectious Disease Research Institute, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Parish","sequence":"additional","affiliation":[{"name":"TB Discovery Research, Infectious Disease Research Institute, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher B.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Global Alliance for TB Drug Development, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Gerard","family":"Waters","sequence":"additional","affiliation":[{"name":"Global Alliance for TB Drug Development, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenkun","family":"Ma","sequence":"additional","affiliation":[{"name":"Global Alliance for TB Drug Development, New York, New York, USA"}],"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, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Sacchettini","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Texas A&amp;M University, College Station, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaqu\u00edn","family":"Rullas","sequence":"additional","affiliation":[{"name":"Tres Cantos Medicines Development Campus, GlaxoSmithKline, Tres Cantos, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I\u00f1igo","family":"Angulo-Barturen","sequence":"additional","affiliation":[{"name":"Tres Cantos Medicines Development Campus, GlaxoSmithKline, Tres Cantos, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"P\u00e9rez-Herr\u00e1n","sequence":"additional","affiliation":[{"name":"Tres Cantos Medicines Development Campus, GlaxoSmithKline, Tres Cantos, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Tres Cantos Medicines Development Campus, GlaxoSmithKline, Tres Cantos, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Barros","sequence":"additional","affiliation":[{"name":"Tres Cantos Medicines Development Campus, GlaxoSmithKline, Tres Cantos, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Cusack","sequence":"additional","affiliation":[{"name":"European Molecular Biology Laboratory, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob J.","family":"Plattner","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. R. K.","family":"Alley","sequence":"additional","affiliation":[{"name":"Anacor Pharmaceuticals, Palo Alto, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.64.1.202-236.2000"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2011.08.049"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.27.4.495"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi9603027"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.10.2351"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/14.19.7529"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00098-4"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2317"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1142189"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889893005588"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444994003112"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444905001617"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20051249"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/8263"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904019158"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909042073"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.5.1004"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060531"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075245"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-207-6_11"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02058-12"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.6.2294-2301.2005"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01423-09"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/35016103"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.2.783-785.2003"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.04.073"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03774-14"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1201964"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi970962r"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/0303-2647(87)90006-2"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi047901v"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq374"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00414-06"},{"key":"e_1_3_3_35_2","first-page":"769","article-title":"Streptomycin treatment of pulmonary tuberculosis","author":"British Medical Journal","year":"1948","unstructured":"British Medical Journal. 1948. Streptomycin treatment of pulmonary tuberculosis. Br Med J ii:769\u2013782.","journal-title":"Br Med J"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.57.4.459-464.1949"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-3879(50)80136-8"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1159\/000237838"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01339-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01339-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T23:11:04Z","timestamp":1645485064000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01339-16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":37,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1128\/AAC.01339-16"],"URL":"https:\/\/doi.org\/10.1128\/aac.01339-16","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10]]},"assertion":[{"value":"2016-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-07-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-09-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}