{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:27:08Z","timestamp":1785403628305,"version":"3.56.0"},"reference-count":47,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"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"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The incidence and endemic range of human babesiosis are expanding. Standard therapy for human babesiosis consists of antimicrobials developed for other indications. While these treatments are adequate in immunocompetent hosts, infections in the immunocompromised can be severe, relapsing, and drug-resistant despite the use of multi-drug regimens. Existing drugs are ineffective in the immunocompromised because they cannot achieve and maintain adequate serum concentrations to inhibit\n                      <jats:italic toggle=\"yes\">Babesia<\/jats:italic>\n                      . Discovery of improved agents against\n                      <jats:italic toggle=\"yes\">Babesia<\/jats:italic>\n                      spp. is of growing importance, and efficient techniques for high-throughput compound screening can assist in this effort. We developed a high-throughput\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      drug screening assay for\n                      <jats:italic toggle=\"yes\">Babesia duncani<\/jats:italic>\n                      that is conducted in 384-well plates and makes use of the fluorescent DNA stain propidium iodide (PI) with relative fluorescence measured by a microplate reader. A Z\u2032 factor of 0.82 was calculated, which suggests an excellent ability to detect inhibitory compounds. A screen of the 41-compound library Structural Genomics Consortium Bug Box was conducted, yielding five hits: trimethoprim, atovaquone, SDDC M7, diphenyleneiodonium chloride, and panobinostat. Panobinostat, a histone deacetylase complex (HDAC) inhibitor, was selected for further evaluation given that its target had not been previously explored in\n                      <jats:italic toggle=\"yes\">B. duncani<\/jats:italic>\n                      . Dose-response testing of structurally related compounds revealed multiple potential leads, including nanatinostat and quisinostat, both of which were potent at the nanomolar level and showed favorable selectivity index in cytotoxicity studies. High-throughput screening using PI and 384-well plates is an advance in drug discovery for babesiosis, and HDAC inhibitors show promise as lead compounds worthy of further investigation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00035-25","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T10:01:54Z","timestamp":1749463314000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["A propidium iodide-based\n                    <i>in vitro<\/i>\n                    screen of the \u201cBug Box\u201d against\n                    <i>Babesia duncani<\/i>\n                    reveals potent inhibitors"],"prefix":"10.1128","author":[{"given":"Emmett A.","family":"Dews","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0155zta11","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of Vermont Larner College of Medicine","place":["Burlington, USA"]},{"id":[{"id":"https:\/\/ror.org\/0155zta11","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Molecular Genetics Master\u2019s Program, University of Vermont","place":["Burlington, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 E.","family":"Teixeira","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0155zta11","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of Vermont Larner College of Medicine","place":["Burlington, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Huston","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0155zta11","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of Vermont Larner College of Medicine","place":["Burlington, USA"]},{"id":[{"id":"https:\/\/ror.org\/0155zta11","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Molecular Genetics Master\u2019s Program, University of Vermont","place":["Burlington, USA"]},{"id":[{"id":"https:\/\/ror.org\/0155zta11","id-type":"ROR","asserted-by":"publisher"}],"name":"Cell, Molecular, and Biomedical Sciences Graduate Program, University of Vermont","place":["Burlington, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin J.","family":"Meyers","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01p7jjy08","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Saint Louis University","place":["St. Louis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8810-1230","authenticated-orcid":true,"given":"Peter R.","family":"Hyson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0155zta11","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, University of Vermont Larner College of Medicine","place":["Burlington, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.ss6806a1"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10111447"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.4920"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1202018"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011151"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/525852"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/649859"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idcr.2022.e01460"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.AC118.005771"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.4103\/ijmr.IJMR_1688_15"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.2307\/3283623"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.2307\/3285750"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1314291"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0125276"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2016.07.032"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00022-14"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiac181"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aba8412"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/108705719900400206"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-023-01360-8"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm200388e"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7211a1"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00662-21"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-11575-5"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx277"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.10.010"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1875-9114.1981.tb03548.x"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","unstructured":"Mayclin SJ Fairman JW Dranow DM Conrady DG Lukacs CM Lorimer DD Horanyi PS Edwards TE Abendroth J. 2021. Crystal structure of dihydrofolate reductase from Mycobacterium tuberculosis bound to NADP and SDDC inhibitor SDDC-M7. Available from: https:\/\/doi.org\/10.2210\/pdb5SCO\/pdb","DOI":"10.2210\/pdb5sco\/pdb"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18071414"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-020-0382-4"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114886"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2009.02.019"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.3390\/ddc3010006"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2012.06.026"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.0c00853"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2015.05.004"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c02104"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph3092751"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15615-z"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-017-2091-y"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14153709"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-11-0044"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1101\/2022.11.09.515859:2022.11.09.515859"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010330"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-3165"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01087"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-2430"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00035-25","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00035-25","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T10:01:58Z","timestamp":1749463318000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00035-25"}},"subtitle":[],"editor":[{"given":"Audrey","family":"Odom John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,6,9]]},"references-count":47,"alternative-id":["10.1128\/aac.00035-25"],"URL":"https:\/\/doi.org\/10.1128\/aac.00035-25","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.01.14.633027","asserted-by":"object"}]},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,9]]},"assertion":[{"value":"2025-01-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00035-25"}}