{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:31:11Z","timestamp":1790213471512,"version":"4.1.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,7,10]],"date-time":"2018-07-10T00:00:00Z","timestamp":1531180800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI116525"],"award-info":[{"award-number":["AI116525"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1181207"],"award-info":[{"award-number":["OPP1181207"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"DOI":"10.3389\/fmicb.2018.01547","type":"journal-article","created":{"date-parts":[[2018,7,10]],"date-time":"2018-07-10T04:52:27Z","timestamp":1531198347000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":47,"title":["MmpL3 as a Target for the Treatment of Drug-Resistant Nontuberculous Mycobacterial Infections"],"prefix":"10.3389","volume":"9","author":[{"given":"Wei","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira","family":"Yazidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitkumar N.","family":"Pandya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Hegde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius","family":"Calado Nogueira de Moura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Jeffrey","family":"North","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurgen","family":"Sygusch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,7,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1021\/acsinfecdis.6b00095","article-title":"Structure-Function profile of MmpL3, the essential mycolic acid transporter from Mycobacterium tuberculosis","volume":"2","author":"Belardinelli","year":"2016","journal-title":"ACS Infect. Dis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.2174\/0929867023368953","article-title":"BM 212 and its derivatives as a new class of antimycobacterial active agents","volume":"9","author":"Biava","year":"2002","journal-title":"Curr. Med. Chem"},{"key":"B3","first-page":"2983","article-title":"New pyrrole derivatives as antimycobacterial agents analogs of BM212. Bioorg. Med. Chem","volume":"9","author":"Biava","year":"1999","journal-title":"Lett"},{"key":"B4","doi-asserted-by":"publisher","first-page":"65","DOI":"10.2174\/138955707779317786","article-title":"New derivatives of BM212: A class of antimycobacterial compounds based on the pyrrole ring as a scaffold","volume":"7","author":"Biava","year":"2007","journal-title":"Mini-Rev. Med. Chem"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1016\/j.bmc.2004.11.018","article-title":"Antimycobacterial compounds. Optimization of the BM 212 structure, the lead compound for a new pyrrole derivative class","volume":"13","author":"Biava","year":"2005","journal-title":"Bioorg. Med. Chem"},{"key":"B6","doi-asserted-by":"publisher","first-page":"5585","DOI":"10.1016\/j.bmc.2011.07.034","article-title":"The structure-activity relationship of urea derivatives as anti-tuberculosis agents","volume":"19","author":"Brown","year":"2011","journal-title":"Bioorg. Med. Chem"},{"key":"B7","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1128\/CMR.05030-11","article-title":"Antimicrobial susceptibility testing, drug resistance mechanisms, and therapy of infections with nontuberculous mycobacteria","volume":"25","author":"Brown-Elliott","year":"2012","journal-title":"Clin. Microbiol. Rev"},{"key":"B8","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1126\/science.aaf8156","article-title":"Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium","volume":"354","author":"Bryant","year":"2016","journal-title":"Science"},{"key":"B9","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1186\/1471-2105-13-S4-S1","article-title":"Accurate multiple sequence alignment of transmembrane proteins with PSI-Coffee","volume":"13","author":"Chang","year":"2012","journal-title":"BMC Bioinformatics"},{"key":"B10","doi-asserted-by":"publisher","first-page":"15006","DOI":"10.1038\/nmicrobiol.2015.6","article-title":"THPP target assignment reveals EchA6 as an essential fatty acid shuttle in mycobacteria","volume":"1","author":"Cox","year":"2016","journal-title":"Nat. Microbiol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"43495","DOI":"10.1038\/srep43495","article-title":"Essentiality of mmpL3 and impact of its silencing on Mycobacterium tuberculosis gene expression","volume":"7","author":"Degiacomi","year":"2017","journal-title":"Sci. Rep"},{"key":"B12","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1111\/mmi.13406","article-title":"A new piperidinol derivative targeting mycolic acid transport","volume":"101","author":"Dupont","year":"2016","journal-title":"Mycobacterium abscessus. Mol. Microbiol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"E7073","DOI":"10.1073\/pnas.1521988112","article-title":"Antiinfectives targeting enzymes and the proton motive force","volume":"112","author":"Feng","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B14","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1136\/thoraxjnl-2015-207983","article-title":"US Cystic fibrosis foundation and european cystic fibrosis society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis: executive summary","volume":"71","author":"Floto","year":"2016","journal-title":"Thorax"},{"key":"B15","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1021\/acsinfecdis.6b00052","article-title":"Diphenylether-Modified 1,2-Diamines with improved drug properties for development against Mycobacterium tuberculosis. ACS Infect","volume":"2","author":"Foss","year":"2016","journal-title":"Dis"},{"key":"B16","doi-asserted-by":"publisher","first-page":"3746","DOI":"10.1016\/j.bmc.2017.05.015","article-title":"Design, synthesis and evaluation of indole-2-carboxamides with pan anti-mycobacterial activity","volume":"25","author":"Franz","year":"2017","journal-title":"Bioorg. Med. Chem"},{"key":"B17","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1038\/nchembio.794","article-title":"Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane","volume":"8","author":"Grzegorzewicz","year":"2012","journal-title":"Nat. Chem. Biol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1093\/cid\/ciq237","article-title":"Clinical and microbiologic outcomes in patients receiving treatment for Mycobacterium abscessus pulmonary disease","volume":"52","author":"Jarand","year":"2011","journal-title":"Clin. Infect. Dis"},{"key":"B19","doi-asserted-by":"publisher","first-page":"8849","DOI":"10.1021\/jm4012774","article-title":"Design, synthesis, and biological evaluation of Indole-2-carboxamides: a promising class of antituberculosis agents","volume":"56","author":"Kondreddi","year":"2013","journal-title":"J. Med. Chem."},{"key":"B20","doi-asserted-by":"publisher","first-page":"5876","DOI":"10.1021\/acs.jmedchem.7b00582","article-title":"Targeting mycolic acid transport by Indole-2-carboxamides for the treatment of Mycobacterium abscessus infections","volume":"60","author":"Kozikowski","year":"2017","journal-title":"J. Med. Chem"},{"key":"B21","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1128\/AAC.05270-11","article-title":"MmpL3 is the cellular target of the antitubercular pyrrole derivative BM212","volume":"56","author":"La Rosa","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"B22","doi-asserted-by":"publisher","first-page":"3126","DOI":"10.1021\/jm500131s","article-title":"Multi-target drug discovery for tuberculosis and other infectious diseases","volume":"57","author":"Li","year":"2014","journal-title":"J. Med. Chem"},{"key":"B23","doi-asserted-by":"publisher","first-page":"5198","DOI":"10.1128\/AAC.00826-16","article-title":"Therapeutic potential of the Mycobacterium tuberculosis mycolic acid transporter, MmpL3","volume":"60","author":"Li","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e02399","DOI":"10.1128\/AAC.02399-16","article-title":"Synergistic interactions of mmpl3 inhibitors with antitubercular compounds in vitro","volume":"61","author":"Li","year":"2017","journal-title":"Antimicrob. Agents Chemother"},{"key":"B25","doi-asserted-by":"publisher","first-page":"6413","DOI":"10.1128\/AAC.03229-14","article-title":"Novel insights into the mechanism of inhibition of MmpL3, a target of multiple pharmacophores in Mycobacterium tuberculosis. Antimicrob","volume":"58","author":"Li","year":"2014","journal-title":"Agents Chemother"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.3389\/fmicb.2017.01539","article-title":"Screening of TB actives for activity against nontuberculous mycobacteria delivers high hit rates","volume":"8","author":"Low","year":"2017","journal-title":"Front. Microbiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2907","DOI":"10.1038\/ncomms3907","article-title":"Indoleamides are active against drug-resistant Mycobacterium tuberculosis","volume":"4","author":"Lun","year":"2013","journal-title":"Nat. Commun"},{"key":"B28","doi-asserted-by":"publisher","first-page":"3616","DOI":"10.1128\/AAC.47.11.3616-3619.2003","article-title":"Resazurin microtiter assay plate testing of Mycobacterium tuberculosis susceptibilities to second-line drugs: rapid, simple, and inexpensive method","volume":"47","author":"Martin","year":"2003","journal-title":"Antimicrob. Agents Chemother"},{"key":"B29","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.ccm.2015.11.001","article-title":"Nontuberculous mycobacterial infections in cystic fibrosis","volume":"37","author":"Martiniano","year":"2016","journal-title":"Clin. Chest. Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3828","DOI":"10.1128\/AAC.02448-14","article-title":"Lack of antimicrobial bactericidal activity","volume":"58","author":"Maurer","year":"2014","journal-title":"Mycobacterium abscessus. Antimicrob. Agents Chemother"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2587","DOI":"10.1016\/j.bmc.2013.02.028","article-title":"Design, synthesis and anti-tuberculosis activity of 1-adamantyl-3-heteroaryl ureas with improved in vitro pharmacokinetic properties","volume":"21","author":"North","year":"2013","journal-title":"Bioorg. Med. Chem"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.1016\/j.ejmech.2010.01.046","article-title":"Synthesis and evaluation of SQ109 analogues as potential anti-tuberculosis candidates","volume":"45","author":"Onajole","year":"2010","journal-title":"Eur. J. Med. Chem"},{"key":"B33","doi-asserted-by":"publisher","first-page":"4093","DOI":"10.1021\/jm4003878","article-title":"Preliminary structure-activity relationships and biological evaluation of novel antitubercular indolecarboxamide derivatives against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains","volume":"56","author":"Onajole","year":"2013","journal-title":"J. Med. Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1055\/s-0035-1546751","article-title":"Nontuberculous mycobacteria in cystic fibrosis and non-cystic fibrosis bronchiectasis","volume":"36","author":"Park","year":"2015","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.jcf.2015.03.012","article-title":"Emerging bacterial pathogens and changing concepts of bacterial pathogenesis in cystic fibrosis","volume":"14","author":"Parkins","year":"2015","journal-title":"J. Cyst. Fibros"},{"key":"B36","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.ejmech.2017.12.075","article-title":"In vivo potent BM635 analogue with improved drug-like properties","volume":"145","author":"Poce","year":"2018","journal-title":"Eur. J. Med. Chem"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.2174\/1389557516666160118105319","article-title":"MmpL3 inhibitors: diverse chemical scaffolds inhibit the same target","volume":"16","author":"Poce","year":"2016","journal-title":"Mini-Rev. Med. Chem"},{"key":"B38","doi-asserted-by":"publisher","first-page":"214r","DOI":"10.1126\/scitranslmed.3007355","article-title":"Indolcarboxamide is a preclinical candidate for treating multidrug-resistant tuberculosis","volume":"5","author":"Rao","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"e60933","DOI":"10.1371\/journal.pone.0060933","article-title":"Tetrahydropyrazolo[1,5-a]Pyrimidine-3-Carboxamide and N-Benzyl-6',7'-Dihydrospiro[Piperidine-4,4'-Thieno[3,2-c] Pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3","volume":"8","author":"Remuinan","year":"2013","journal-title":"PLoS ONE"},{"key":"B40","doi-asserted-by":"publisher","first-page":"823","DOI":"10.2217\/fmb.12.56","article-title":"Discovery and development of SQ109: a new antitubercular drug with a novel mechanism of action","volume":"7","author":"Sacksteder","year":"2012","journal-title":"Future Microbiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"3255","DOI":"10.1016\/j.bmc.2012.03.058","article-title":"Screening a library of 1600 adamantyl ureas for anti-Mycobacterium tuberculosis activity in vitro and for better physical chemical properties for bioavailability","volume":"20","author":"Scherman","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"B42","doi-asserted-by":"publisher","first-page":"6232","DOI":"10.1021\/acs.jmedchem.6b00415","article-title":"Indole-2-carboxamide-based MmpL3 inhibitors show exceptional antitubercular activity in an animal model of tuberculosis infection","volume":"59","author":"Stec","year":"2016","journal-title":"J. Med. Chem"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1128\/AAC.05708-11","article-title":"SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis","volume":"56","author":"Tahlan","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"B44","doi-asserted-by":"publisher","first-page":"7993","DOI":"10.1073\/pnas.1700062114","article-title":"MmpL3 is the flippase or mycolic acids in mycobacteria","volume":"114","author":"Xu","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B45","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/nmeth.3213","article-title":"The I-TASSER suite: protein structure and function prediction","volume":"12","author":"Yang","year":"2015","journal-title":"Nat. Methods"},{"key":"B46","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1021\/ml400071a","article-title":"Discovery of tetrahydropyrazolopyrimidine carboxamide derivatives as potent and orally active antitubercular agents","volume":"4","author":"Yokokawa","year":"2013","journal-title":"ACS Med. Chem. Lett"},{"key":"B47","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1471-2105-9-40","article-title":"I-TASSER server for protein 3D structure prediction","volume":"9","author":"Zhang","year":"2008","journal-title":"BMC Bioinformatics"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fmicb.2018.01547\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,7,10]],"date-time":"2018-07-10T04:52:34Z","timestamp":1531198354000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fmicb.2018.01547\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,10]]},"references-count":47,"alternative-id":["10.3389\/fmicb.2018.01547"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2018.01547","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,10]]},"article-number":"1547"}}