{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T12:00:44Z","timestamp":1787832044601,"version":"build-2784847793"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2017R1A2A2A05069562, NRF-2021R1A2C2008235, NRF-R1A4A1031574"],"award-info":[{"award-number":["NRF-2017R1A2A2A05069562, NRF-2021R1A2C2008235, NRF-R1A4A1031574"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U.K. Medical Research Council and Department for International Development and a Wellcome Trust Discovery Awards","award":["MR\/M021157\/1, 225844\/Z\/22\/Z"],"award-info":[{"award-number":["MR\/M021157\/1, 225844\/Z\/22\/Z"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,5,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The absence of an\n              <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n              cultivation system for\n              <jats:italic toggle=\"yes\">Plasmodium vivax<\/jats:italic>\n              hinders the exploration of molecular targets for vaccine development. To address this, functional studies often rely on alternative models, such as\n              <jats:italic toggle=\"yes\">P. knowlesi<\/jats:italic>\n              , due to its genetic similarity to\n              <jats:italic toggle=\"yes\">P. vivax<\/jats:italic>\n              . This study investigated the role of a novel micronemal protein, PvMP38 (PVX_110945), in both\n              <jats:italic toggle=\"yes\">P. vivax<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">P. knowlesi<\/jats:italic>\n              merozoite invasion of erythrocytes. The full-length ectodomain of PvMP38 was expressed, and polyclonal antibodies were generated to assess its function. PvMP38 was confirmed to localize on micronemal organelle in both\n              <jats:italic toggle=\"yes\">P. vivax<\/jats:italic>\n              and\n              <jats:italic toggle=\"yes\">P. knowlesi<\/jats:italic>\n              merozoites.\n              <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n              protein-protein interaction assays revealed that PvMP38 binds to Pv12 with high-affinity interaction. A conserved novel complex of Pv12-Pv41-PvMP38 was identified by immunoprecipitation of\n              <jats:italic toggle=\"yes\">P. vivax<\/jats:italic>\n              antibodies on\n              <jats:italic toggle=\"yes\">P. knowlesi<\/jats:italic>\n              schizont lysates. Linear epitopes of PvMP38 with high and moderate antigenicity were identified in clinical isolates of both species. Invasion inhibition assays demonstrated that a triple antibody combination targeting the PvMP38, Pv12, and Pv41 significantly reduced\n              <jats:italic toggle=\"yes\">P. knowlesi<\/jats:italic>\n              merozoite invasion of erythrocytes compared to a single antibody. In addition, CRISPR\/Cas9-mediated knockout of\n              <jats:italic toggle=\"yes\">P. knowlesi mp38<\/jats:italic>\n              markedly impaired parasite growth, underscoring its essential role during the asexual stage. These findings identify PvMP38 and its associated complex as promising targets for malaria interventions and highlight the utility of\n              <jats:italic toggle=\"yes\">P. knowlesi<\/jats:italic>\n              as a model for investigating\n              <jats:italic toggle=\"yes\">P. vivax<\/jats:italic>\n              erythrocyte invasion mechanisms.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                This manuscript reported an effort in malaria eradication by identifying and functionally characterizing a novel\n                <jats:italic toggle=\"yes\">Plasmodium vivax<\/jats:italic>\n                micronemal protein, PvMP38, involved in erythrocyte invasion. A narrow repertoire of an efficacious vaccine targeting\n                <jats:italic toggle=\"yes\">P. vivax<\/jats:italic>\n                candidates is being developed due to the lack of continuous\n                <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                culture. This study addresses a gap in\n                <jats:italic toggle=\"yes\">P. vivax<\/jats:italic>\n                research using\n                <jats:italic toggle=\"yes\">P. knowlesi<\/jats:italic>\n                as a model for both genome editing and antibody functionality validation. By enhancing the protein-protein interaction screening framework, this study demonstrated that PvMP38 forms a complex with Pv12 and Pv41, opening the approaches to multi-antigen vaccines. The successful application of CRISPR\/Cas9 gene editing techniques to disrupt its homolog, the\n                <jats:italic toggle=\"yes\">pkmp38<\/jats:italic>\n                gene, further assesses the protein\u2019s significance in the growth and invasion of the parasite. These findings provided valuable insights into the biology of\n                <jats:italic toggle=\"yes\">P. vivax<\/jats:italic>\n                and proposed PvMP38 as a promising candidate for malaria intervention strategies.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/mbio.03917-24","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T13:01:23Z","timestamp":1744203683000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["A novel micronemal protein MP38 is involved in the invasion of merozoites into erythrocytes"],"prefix":"10.1128","volume":"16","author":[{"given":"Tuyet-Kha","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine","place":["Chuncheon-si, South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sy-Thau","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine","place":["Chuncheon-si, South Korea"]},{"name":"Institue of Clinical Infectious Diseases, 108 Military Central Hospital","place":["Hanoi, Vietnam"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Van-Truong","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine","place":["Chuncheon-si, South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Hun","family":"Na","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kangwon National University School of Medicine","place":["Chuncheon-si, South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9070-4292","authenticated-orcid":true,"given":"Robert W.","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jetsumon","family":"Sattabongkot","sequence":"additional","affiliation":[{"name":"Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University","place":["Bangkok, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee Ling","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Faculty of Medicine, Universiti Malaya","place":["Kuala Lumpur, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Sun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Kangwon National University","place":["Chuncheon-si, South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Joo","family":"Chun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Kangwon National University","place":["Chuncheon-si, South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology and Immunology, School of Medicine, Yangzhou University","place":["Yangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-Kyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine","place":["Chuncheon-si, South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0836-6675","authenticated-orcid":true,"given":"Jin-Hee","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine","place":["Chuncheon-si, South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1962-7199","authenticated-orcid":true,"given":"Eun-Taek","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Medical Environmental Biology and Tropical Medicine, Kangwon National University School of Medicine","place":["Chuncheon-si, South Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.smj.0000189904.50838.eb"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03612.x"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/14760584.2021.1880898"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adf1782"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003644"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/424852"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.1.43-49.1999"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2018.10.002"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1008115"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004708"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2008.02.007"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0008323"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008864"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00079-12"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.45829"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.O113.028357"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004264"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.parint.2012.02.008"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2013.03.002"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1145213"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09098-w"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-021-00939-3"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2316304121"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01117-12"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2014.02.029"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1354880"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep35581"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep26993"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-017-1837-5"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.3347\/kjp.2016.54.6.725"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-018-2420-4"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23728-1"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100662"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007470"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041937"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.916702"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.04.080"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.2.e9"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot4977"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-023-06031-5"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.62"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/pr100705g"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1216457110"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1522469113"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40357-z"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.3522"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3015"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-7-45"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03917-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mbio.03917-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T13:02:12Z","timestamp":1747227732000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mbio.03917-24"}},"subtitle":[],"editor":[{"given":"L. David","family":"Sibley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Niraj Harish","family":"Tolia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,5,14]]},"references-count":48,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5,14]]}},"alternative-id":["10.1128\/mbio.03917-24"],"URL":"https:\/\/doi.org\/10.1128\/mbio.03917-24","relation":{},"ISSN":["2150-7511"],"issn-type":[{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,14]]},"assertion":[{"value":"2025-01-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03917-24"}}