{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:39:38Z","timestamp":1792510778830,"version":"4.5.0"},"reference-count":49,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201018\u2010IdEx\u20100001"],"award-info":[{"award-number":["ANR\u201018\u2010IdEx\u20100001"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"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                      <jats:italic toggle=\"yes\">Plasmodium falciparum<\/jats:italic>\n                      resistance to current first-line treatments is threatening at-risk populations and underscores the urgent need for novel therapeutic targets and drugs.\n                      <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                      pyruvate kinases I and II are two essential enzymes with distinct roles and subcellular localizations within the parasite.\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PyrKI is cytosolic, while\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PyrKII is found in the apicoplast, a specific organelle of\n                      <jats:italic toggle=\"yes\">Apicomplexa<\/jats:italic>\n                      , where it is required for the production of (d)NTPs essential for apicoplast maintenance. We identify skeletocutin E, a basidiomycete-derived metabolite, as a specific inhibitor of\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PyrKII. Skeletocutin E inhibits\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      the activity of\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PyrKII with an IC\n                      <jats:sub>50<\/jats:sub>\n                      of 0.52 \u00b1 0.08 \u00b5M through a mixed inhibition mechanism and does not affect the activities of three human pyruvate kinases. Structure\u2013activity relationship analyses using synthetic skeletocutin E analogs allowed us to identify the molecular determinants of this inhibition. Furthermore, determination of the quaternary structure of\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PyrKII by mass photometry showed that skeletocutin E does not alter the distribution of the complexes, indicating that it does not interact at the subunit interfaces. We addressed the expression of\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PyrKII in liver stages and confirmed its apicoplast localization. Importantly, skeletocutin E inhibits\n                      <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                      growth in both blood and liver stages, with IC\n                      <jats:sub>\u2085\u2080<\/jats:sub>\n                      values of 3.56 \u00b1 0.50 \u00b5M in red blood cells and 3.70 \u00b1 0.74 \u00b5M in primary human hepatocytes. Together, these findings establish\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      PyrKII as a druggable antimalarial target and identify skeletocutin E as a promising lead compound for the rational development of dual-stage antimalarial therapies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00160-26","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:50:05Z","timestamp":1792507805000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Dual-stage inhibition of\n                    <i>Plasmodium falciparum<\/i>\n                    by a\n                    <i>Skeletocutis<\/i>\n                    -derived fungal metabolite targeting pyruvate kinase II"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0788-6985","authenticated-orcid":false,"given":"Lucille","family":"Herv\u00e9","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"MERIT, Universit\u00e9 Paris Cit\u00e9, IRD, Inserm","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Amanzougaghene","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02en5vm52","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Sorbonne Universit\u00e9, INSERM, CNRS","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"Amand","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wkt5x30","id-type":"ROR","asserted-by":"publisher"}],"name":"Mol\u00e9cules de Communication et Adaptation des Micro-Organismes UMR 7245, Mus\u00e9um National d'Histoire Naturelle, CNRS","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shany","family":"Achache","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"MERIT, Universit\u00e9 Paris Cit\u00e9, IRD, Inserm","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Blaud","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"CiTCoM, Universit\u00e9 Paris Cit\u00e9, CNRS","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3024-5928","authenticated-orcid":true,"given":"Romain","family":"Copp\u00e9e","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03fdnmv92","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre National de R\u00e9f\u00e9rence du Paludisme, AP-HP, H\u00f4pital Bichat Claude-Bernard","place":["Paris, France"]},{"id":[{"id":"https:\/\/ror.org\/04cdk4t75","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre National de R\u00e9f\u00e9rence Cryptosporidioses, Microsporidies et Autres Protozooses Digestives, Institut de Biologie Clinique, Centre Hospitalier Universitaire de Rouen","place":["Rouen, France"]},{"id":[{"id":"https:\/\/ror.org\/03nhjew95","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratoire de Parasitologie-Mycologie, UR ESCAPE, Universit\u00e9 de Rouen Normandie","place":["Rouen, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaineb","family":"Fourati","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"CiTCoM, Universit\u00e9 Paris Cit\u00e9, CNRS","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Franetich","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02en5vm52","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Sorbonne Universit\u00e9, INSERM, CNRS","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quentin","family":"Goor","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"MERIT, Universit\u00e9 Paris Cit\u00e9, IRD, Inserm","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9016-3847","authenticated-orcid":true,"given":"Sandrine","family":"Houz\u00e9","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"MERIT, Universit\u00e9 Paris Cit\u00e9, IRD, Inserm","place":["Paris, France"]},{"id":[{"id":"https:\/\/ror.org\/03fdnmv92","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre National de R\u00e9f\u00e9rence du Paludisme, AP-HP, H\u00f4pital Bichat Claude-Bernard","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murielle","family":"Lohezic","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"MERIT, Universit\u00e9 Paris Cit\u00e9, IRD, Inserm","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Patat","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"MERIT, Universit\u00e9 Paris Cit\u00e9, IRD, Inserm","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Sarrasin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"MERIT, Universit\u00e9 Paris Cit\u00e9, IRD, Inserm","place":["Paris, France"]},{"id":[{"id":"https:\/\/ror.org\/03fdnmv92","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre National de R\u00e9f\u00e9rence du Paludisme, AP-HP, H\u00f4pital Bichat Claude-Bernard","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarata","family":"Toure","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02en5vm52","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Sorbonne Universit\u00e9, INSERM, CNRS","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Zelie","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"CiTCoM, Universit\u00e9 Paris Cit\u00e9, CNRS","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Soulard","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02en5vm52","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre d'Immunologie et des Maladies Infectieuses, CIMI-Paris, Sorbonne Universit\u00e9, INSERM, CNRS","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8199-5449","authenticated-orcid":false,"given":"St\u00e9phane","family":"Mann","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03wkt5x30","id-type":"ROR","asserted-by":"publisher"}],"name":"Mol\u00e9cules de Communication et Adaptation des Micro-Organismes UMR 7245, Mus\u00e9um National d'Histoire Naturelle, CNRS","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9756-7980","authenticated-orcid":true,"given":"Ana\u00efs","family":"Merckx","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}],"name":"MERIT, Universit\u00e9 Paris Cit\u00e9, IRD, Inserm","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"key":"e_1_3_3_2_2","unstructured":"WHO. 2025. World malaria report 2025. Available from: https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2025"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2101746"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-4959(03)00081-2"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.238865"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/20406207211066070"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2023.02.005"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867328666210322103340"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.800293"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2380275"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/abbi.2002.2782"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/prep.1998.0938"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3691"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tmaid.2006.01.015"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.50807"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.parint.2008.10.005"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aap7847"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.08.048"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2022.08.001"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-3726-5_3"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr200258w"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.2174\/0929867328666210803152419"},{"key":"e_1_3_3_24_2","doi-asserted-by":"crossref","unstructured":"Fernandes JF Lell B Agnandji ST Obiang RM Bassat Q Kremsner PG Mordm\u00fcller B Grobusch MP. 2015. Fosmidomycin as an antimalarial drug: a meta-analysis of clinical trials. Future Medicine Ltd London UK. Available from: https:\/\/www.futuremedicine.com\/doi\/10.2217\/FMB.15.60","DOI":"10.2217\/FMB.15.60"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2017.12.005"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44386-025-00006-5"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202501449"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01168-19"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo971753f"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.9b02598"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.1c01890"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2024.107112"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003522"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01270.x"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12633"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12485"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00198-14"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001138"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2023.2245168"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1052"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-5-110"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.gr-1522r"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2008.01.001"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.3762\/bjoc.15.270"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo010260e"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph16050705"},{"key":"e_1_3_3_47_2","first-page":"676","article-title":"Enzyme kinetic assay to measure the activity of tumor M2 pyruvate kinase in breast cancer patients","volume":"47","author":"Guan M","year":"2017","unstructured":"Guan M, Tong Y, Liu X, Dong D, Zhou Y. 2017. Enzyme kinetic assay to measure the activity of tumor M2 pyruvate kinase in breast cancer patients. Ann Clin Lab Sci 47:676\u2013686.","journal-title":"Ann Clin Lab Sci"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp253"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.781840"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202101237"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00160-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aac.00160-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:50:08Z","timestamp":1792507808000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aac.00160-26"}},"subtitle":[],"editor":[{"given":"Purnima","family":"Bhanot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,20]]},"references-count":49,"alternative-id":["10.1128\/aac.00160-26"],"URL":"https:\/\/doi.org\/10.1128\/aac.00160-26","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,20]]},"assertion":[{"value":"2026-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00160-26"}}