{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:06:38Z","timestamp":1790395598065,"version":"4.1.0"},"reference-count":74,"publisher":"National Academy of Sciences","issue":"37","license":[{"start":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T00:00:00Z","timestamp":1566432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["U54 AI065359"],"award-info":[{"award-number":["U54 AI065359"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000774","name":"DOD | Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["HDTRA1-11-1-003"],"award-info":[{"award-number":["HDTRA1-11-1-003"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000774","name":"DOD | Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["HDTRA1-17-1-0015"],"award-info":[{"award-number":["HDTRA1-17-1-0015"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["F30AI118342"],"award-info":[{"award-number":["F30AI118342"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM008042"],"award-info":[{"award-number":["T32GM008042"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,9,10]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Burkholderia pseudomallei<\/jats:italic>\n                    , the etiologic agent of melioidosis, is an environmental organism that inhabits tropical soils and kills an estimated 90,000 people each year. Caused by an intracellular and often drug-resistant pathogen, melioidosis is notoriously difficult to treat, with mortality rates approaching 50% in some settings despite appropriate diagnosis and clinical management. Using a high-throughput, cell-based phenotypic screen we have discovered 2 antibiotic candidates with improved in vivo efficacy compared to the current standard of care: a fluoroquinolone analog, burkfloxacin, and an FDA-approved antifungal drug, flucytosine. As a widely used antifungal with a well-known safety profile, the potential to repurpose flucytosine for treating melioidosis may represent a rapid route to clinical translation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1906388116","type":"journal-article","created":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T19:25:14Z","timestamp":1566501914000},"page":"18597-18606","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":17,"title":["An in situ high-throughput screen identifies inhibitors of intracellular\n                    <i>Burkholderia pseudomallei<\/i>\n                    with therapeutic efficacy"],"prefix":"10.1073","volume":"116","author":[{"given":"Philip L.","family":"Bulterys","sequence":"first","affiliation":[{"name":"University of California, Los Angeles\u2013California Institute of Technology Medical Scientist Training Program, David Geffen School of Medicine, University of California, Los Angeles, CA 90095;"},{"name":"Molecular Biology Institute, University of California, Los Angeles, CA 90095;"},{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle J.","family":"Toesca","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Norris","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611;"},{"name":"Emerging Pathogens Institute, University of Florida, Gainesville, FL 32611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey P.","family":"Maloy","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7090-5719","authenticated-orcid":false,"given":"Sorel T.","family":"Fitz-Gibbon","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"France","sequence":"additional","affiliation":[{"name":"California NanoSystems Institute, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babak","family":"Toffig","sequence":"additional","affiliation":[{"name":"California NanoSystems Institute, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Morselli","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawarat","family":"Somprasong","sequence":"additional","affiliation":[{"name":"Emerging Pathogens Institute, University of Florida, Gainesville, FL 32611;"},{"name":"Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA 90095;"},{"name":"California NanoSystems Institute, University of California, Los Angeles, CA 90095;"},{"name":"Institute of Genomics and Proteomics, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert P.","family":"Schweizer","sequence":"additional","affiliation":[{"name":"Emerging Pathogens Institute, University of Florida, Gainesville, FL 32611;"},{"name":"Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apichai","family":"Tuanyok","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611;"},{"name":"Emerging Pathogens Institute, University of Florida, Gainesville, FL 32611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Damoiseaux","sequence":"additional","affiliation":[{"name":"California NanoSystems Institute, University of California, Los Angeles, CA 90095;"},{"name":"Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher T.","family":"French","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095;"},{"name":"California NanoSystems Institute, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff F.","family":"Miller","sequence":"additional","affiliation":[{"name":"Molecular Biology Institute, University of California, Los Angeles, CA 90095;"},{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095;"},{"name":"California NanoSystems Institute, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,8,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2011.02671.x"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003892"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/529290a"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.107"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02444-15"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00660-13"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.12.116"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2016.07.003"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1204699"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2016.263"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-131"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107263450404"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.317.5841.1022"},{"key":"e_1_3_3_14_2","first-page":"99","volume-title":"Bioterrorism and Infectious Agents","author":"Dance D. A.","year":"2005","unstructured":"D. A. Dance, \u201cMelioidosis and glanders as possible biological weapons\u201d in Bioterrorism and Infectious Agents (Springer Science, New York, 2005), pp. 99\u2013145."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2009.10.004"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2014.00429"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00626-08"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2015.8"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000900"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.12.6032-6034.2005"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2010.10-0038"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2014.01.005"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01357-17"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy069"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005209"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.00305"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00263-08"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1107183108"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04528.x"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.112408.134030"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01367-13"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01368-13"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001068"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.10.065"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2017.05.003"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1222901"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0706532104"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510322103"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10846"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00468-17"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01262-05"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01544-14"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01218-10"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2201"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3975"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu392"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1586\/eri.10.4"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00186a014"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm00062a007"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.12.2622"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2015.10.012"},{"key":"e_1_3_3_52_2","first-page":"17","volume-title":"Essential Medicines and Health Products","author":"WHO","year":"2017","unstructured":"WHO, \u201cWHO model list of essential medicines\u201d in Essential Medicines and Health Products, (World Health Organization, Geneva, Switzerland, 2017), pp. 17\u201318."},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-014-0206-6"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.06.002"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/46.2.171"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00604-13"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00463-18"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.8b00678"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2015.07.004"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02446-16"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00082-17"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(08)70025-7"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1086\/428052"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(97)90044-4"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0357-1"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2017.01.004"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3013"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2019.00049"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00217-16"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja105003g"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01974-14"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1093\/gbe\/evq003"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.03.031"},{"key":"e_1_3_3_74_2","unstructured":"KEGG Pyrimidine metabolism- Burkholderia thailandensis E264. https:\/\/www.genome.jp\/dbget-bin\/www_bget?bte00240. Accessed 31 August 2016."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1906388116","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1906388116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T05:11:55Z","timestamp":1649826715000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1906388116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,22]]},"references-count":74,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2019,9,10]]}},"alternative-id":["10.1073\/pnas.1906388116"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1906388116","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,22]]},"assertion":[{"value":"2019-08-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}