{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:02:41Z","timestamp":1791460961474,"version":"4.3.4"},"reference-count":91,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6734","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2025,2,7]]},"abstract":"<jats:p>\n                    Measures to combat the parasites that cause malaria have become compromised because of reliance on a small arsenal of drugs and emerging drug resistance. We conducted a transposon mutagenesis screen in the primate malaria parasite\n                    <jats:italic>Plasmodium knowlesi<\/jats:italic>\n                    , producing the most complete classification of gene essentiality in any\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    spp. to date, with the resolution to define truncatable genes. We found conservation in the druggable genome between\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    spp. and divergences in mitochondrial metabolism. Perturbation analyses with the frontline antimalarial artemisinin revealed modulators that both increase and decrease drug susceptibility. Our findings aid prioritization of drug and vaccine targets for the\n                    <jats:italic>Plasmodium vivax<\/jats:italic>\n                    clade and reveal mechanisms of resistance that can inform therapeutic development.\n                  <\/jats:p>","DOI":"10.1126\/science.adq6241","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T13:59:31Z","timestamp":1738850371000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":36,"title":["The essential genome of\n                    <i>Plasmodium knowlesi<\/i>\n                    reveals determinants of antimalarial susceptibility"],"prefix":"10.1126","volume":"387","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7025-7835","authenticated-orcid":true,"given":"Brendan","family":"Elsworth","sequence":"first","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA."},{"name":"Laboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7206-1502","authenticated-orcid":true,"given":"Sida","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA."},{"name":"Department of Mathematics, University of Massachusetts Boston, Boston, MA, USA."},{"name":"Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7694-8867","authenticated-orcid":true,"given":"Sheena","family":"Dass","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5015-4740","authenticated-orcid":true,"given":"Jacob A.","family":"Tennessen","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qudseen","family":"Sultana","sequence":"additional","affiliation":[{"name":"Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, USA."},{"name":"Department of Computer Science, University of Massachusetts Boston, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7655-2440","authenticated-orcid":true,"given":"Basil T.","family":"Thommen","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4123-7410","authenticated-orcid":true,"given":"Aditya S.","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3169-4557","authenticated-orcid":true,"given":"Usheer","family":"Kanjee","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Gr\u00fcring","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5293-9090","authenticated-orcid":true,"given":"Marcelo U.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil."},{"name":"Global Health and Tropical Medicine, Institute of Hygiene and Tropical Medicine, Nova University of Lisbon, Lisbon, Portugal."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2769-8600","authenticated-orcid":true,"given":"Marc-Jan","family":"Gubbels","sequence":"additional","affiliation":[{"name":"Department of Biology, Boston College, Chestnut Hill, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5108-8108","authenticated-orcid":true,"given":"Kourosh","family":"Zarringhalam","sequence":"additional","affiliation":[{"name":"Department of Mathematics, University of Massachusetts Boston, Boston, MA, USA."},{"name":"Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8534-5515","authenticated-orcid":true,"given":"Manoj T.","family":"Duraisingh","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"World Health Organization (WHO) \u201cWorld Malaria Report 2023\u201d (2023); https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2023."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-020-0196-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2022.102193"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2375"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1216457110"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2612"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11332-4"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-022-04130-9"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1008322108"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.200279.115"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aap7847"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007809"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.06.030"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.019"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1314533"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008864"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.45829"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1522469113"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.740506"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.2.655-660.2002"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1003"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2023.03.016"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2016.11"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00670-12"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12596"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.09.011"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.07.003"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.831592"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40885-8"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010846"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2020.00148"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11187"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.109918"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.1c00322"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2017.11.010"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.07.039"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2210929120"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.3390\/parasitologia2020011"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00209-8"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2016.166"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00696-16"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.6b00025"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2023.09.011"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2020.03.006"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.05014-22"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24814-1"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.178830"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006930"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12876"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0214023"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.269399"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20805-w"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009582"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18624-0"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00540-22"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2023.04.006"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15102440"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00392-22"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.0c00900"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00956-20"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02312-20"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007722"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1806109115"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep13891"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002132"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-6-r56"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02519-17"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005824"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01607-06"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00928-16"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.11.4097-4102.2004"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.14806\/ej.17.1.200"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq033"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-303"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky431"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1224503"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msv012"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1832-y"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0201-4"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts356"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw354"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3122"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.23297.1"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx428"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts378"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr509"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.11896.2"},{"key":"e_1_3_2_92_2","unstructured":"S. Ye umbibio\/PkHessentialome: PkH_essentialome version 1.1 Zenodo (2024); https:\/\/doi.org\/10.5281\/zenodo.13852567.10.5281\/zenodo.13852567"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.adq6241","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T06:30:29Z","timestamp":1744871429000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.adq6241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,7]]},"references-count":91,"journal-issue":{"issue":"6734","published-print":{"date-parts":[[2025,2,7]]}},"alternative-id":["10.1126\/science.adq6241"],"URL":"https:\/\/doi.org\/10.1126\/science.adq6241","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,7]]},"assertion":[{"value":"2024-06-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadq6241"}}