{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:17:42Z","timestamp":1785421062096,"version":"3.56.0"},"reference-count":23,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI184855"],"award-info":[{"award-number":["R01 AI184855"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI125534"],"award-info":[{"award-number":["R01AI125534"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2026,7,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Most apicomplexan parasites contain a plastid-derived organelle called the apicoplast, which originated through secondary endosymbiosis. As a result of this evolutionary trajectory, the non-photosynthetic apicoplast is surrounded by four membranes and contains many bacterial-like, druggable targets. It is widely accepted that asexual malaria parasites (\n                      <jats:italic toggle=\"yes\">Plasmodium falciparum<\/jats:italic>\n                      ) can thrive under antibiotic treatment if supplemented with high concentrations of isopentenyl pyrophosphate (IPP, 200 \u00b5M), and these IPP-rescued parasites are thought to lack the apicoplast and its 35 kb genome but possess many vesicles. However, our findings suggest that this \u201capicoplast-minus\u201d concept may warrant reconsideration. Using live-cell microscopy, we observed that apicoplast-derived vesicles closely colocalize with mitochondria in late schizonts and are faithfully segregated into merozoites during schizogony, suggesting that these vesicles are inherited from the previous cycle rather than newly synthesized. Furthermore, immuno-electron microscopy (immuno-EM) revealed that the apicoplast-minus parasites possess structures surrounded by four membranes, in addition to single-membrane-surrounded entities. The presence of four-membrane-bound structures suggests that the apicoplast has not truly disappeared in the apicoplast-minus\n                      <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                      but has remained in a distinct, diminished form. We propose that these distinct four-membrane-bound structures still retain essential biochemical and\/or structural functions, which act as barriers to the complete loss of apicoplast when the parasites face antibiotic stress and IPP rescue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>The plant-like organelle named apicoplast is essential for malaria parasites and is a major antimalarial drug target. For more than a decade, scientists have believed that malaria parasites in the blood stages could dispense with the apicoplast if they were supplied with a critical metabolite made by the organelle, leading to the idea of \u201capicoplast-minus\u201d parasites. Our results challenge this long-standing view. We find that even when the apicoplast is disrupted, the organelle remains in a highly reduced form. This apicoplast-derived organelle is inherited as parasites continue their life cycles, suggesting that it contains essential functions even when the organelle is disrupted. Our data reveal an unexpected level of complexity in apicoplast biology and open new doors for future identification of essential apicoplast-derived pathways that cannot be easily bypassed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00024-26","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T13:01:11Z","timestamp":1782738071000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Inheritance of four-membrane-bound structures in the \u201capicoplast-minus\u201d\n                    <i>Plasmodium falciparum<\/i>"],"prefix":"10.1128","volume":"11","author":[{"given":"Wei","family":"Xu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bdffz58","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Molecular Parasitology, Drexel University College of Medicine","place":["Philadelphia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikechukwu","family":"Nwankwo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bdffz58","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Molecular Parasitology, Drexel University College of Medicine","place":["Philadelphia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9684-1733","authenticated-orcid":false,"given":"Sean T.","family":"Prigge","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2006-3987","authenticated-orcid":true,"given":"Hangjun","family":"Ke","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bdffz58","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Center for Molecular Parasitology, Drexel University College of Medicine","place":["Philadelphia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003335107"},{"key":"e_1_3_2_3_2","first-page":"193","article-title":"The treatment of malaria with tetracycline","volume":"3","author":"Grande EN","year":"1956","unstructured":"Grande EN, Sanchez AR, Sanchez FR. 1956. The treatment of malaria with tetracycline. Antibiotic Med Clin Ther (New York) 3:193\u2013196.","journal-title":"Antibiotic Med Clin Ther (New York)"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/381482a0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5305.1485"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2022.102255"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2016.08.005"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001138"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku500"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.29865"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2005895"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02021-17"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000136"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01492-20"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.58629"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/jeu.12947"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008316"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-66393-5"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-12-25"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020107247"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202406064"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03036-24"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011818"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.012646"}],"container-title":["mSphere"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msphere.00024-26","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/msphere.00024-26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T13:01:56Z","timestamp":1785243716000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/msphere.00024-26"}},"subtitle":[],"editor":[{"given":"Laura A.","family":"Kirkman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":23,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7,28]]}},"alternative-id":["10.1128\/msphere.00024-26"],"URL":"https:\/\/doi.org\/10.1128\/msphere.00024-26","relation":{},"ISSN":["2379-5042"],"issn-type":[{"value":"2379-5042","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]},"assertion":[{"value":"2026-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00024-26"}}