{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T08:44:43Z","timestamp":1790239483609,"version":"4.1.0"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2015,4,10]],"date-time":"2015-04-10T00:00:00Z","timestamp":1428624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"},{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"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"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The emergence of drug-resistant parasites is a serious threat faced by malaria control programs. Understanding the genetic basis of resistance is critical to the success of treatment and intervention strategies. A novel locus associated with antimalarial resistance,\n                    <jats:italic>ap2-mu<\/jats:italic>\n                    (encoding the mu chain of the adaptor protein 2 [AP2] complex), was recently identified in studies on the rodent malaria parasite\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium chabaudi<\/jats:named-content>\n                    (\n                    <jats:italic>pcap2-mu<\/jats:italic>\n                    ). Furthermore, analysis in Kenyan malaria patients of polymorphisms in the\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium falciparum<\/jats:named-content>\n                    <jats:italic>ap2-mu<\/jats:italic>\n                    homologue,\n                    <jats:italic>pfap2-mu<\/jats:italic>\n                    , found evidence that differences in the amino acid encoded by codon 160 are associated with enhanced parasite survival\n                    <jats:italic>in vivo<\/jats:italic>\n                    following combination treatments which included artemisinin derivatives. Here, we characterize the role of\n                    <jats:italic>pfap2-mu<\/jats:italic>\n                    in mediating the\n                    <jats:italic>in vitro<\/jats:italic>\n                    antimalarial drug response of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>\n                    by generating transgenic parasites constitutively expressing codon 160 encoding either the wild-type Ser (Ser160) or the Asn mutant (160Asn) form of\n                    <jats:italic>pfap2-mu<\/jats:italic>\n                    . Transgenic parasites carrying the\n                    <jats:italic>pfap2-mu<\/jats:italic>\n                    160Asn allele were significantly less sensitive to dihydroartemisinin using a standard 48-h\n                    <jats:italic>in vitro<\/jats:italic>\n                    test, providing direct evidence of an altered parasite response to artemisinin. Our data also provide evidence that\n                    <jats:italic>pfap2-mu<\/jats:italic>\n                    variants can modulate parasite sensitivity to quinine. No evidence was found that\n                    <jats:italic>pfap2-mu<\/jats:italic>\n                    variants contribute to the slow-clearance phenotype exhibited by\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>\n                    in Cambodian patients treated with artesunate monotherapy. These findings provide compelling evidence that\n                    <jats:italic>pfap2-mu<\/jats:italic>\n                    can modulate\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>\n                    responses to multiple drugs. We propose that this gene should be evaluated further as a potential molecular marker of antimalarial resistance.\n                  <\/jats:p>","DOI":"10.1128\/aac.04067-14","type":"journal-article","created":{"date-parts":[[2015,2,17]],"date-time":"2015-02-17T22:01:46Z","timestamp":1424210506000},"page":"2540-2547","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":54,"title":["The Mu Subunit of Plasmodium falciparum Clathrin-Associated Adaptor Protein 2 Modulates\n                    <i>In Vitro<\/i>\n                    Parasite Response to Artemisinin and Quinine"],"prefix":"10.1128","volume":"59","author":[{"given":"Gisela","family":"Henriques","sequence":"first","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donelly A.","family":"van Schalkwyk","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebekah","family":"Burrow","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Warhurst","sequence":"additional","affiliation":[{"name":"Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloise","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Fidock","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Hallett","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Flueck","sequence":"additional","affiliation":[{"name":"Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin J.","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom"},{"name":"Department of Clinical Parasitology, Hospital for Tropical Diseases, University College London Hospital, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0805011"},{"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":"10.1126\/science.1215966"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314981"},{"key":"e_1_3_3_6_2","unstructured":"WHO. 2014. Status report on artemisinin resistance. World Health Organization Geneva Switzerland. http:\/\/www.who.int\/malaria\/publications\/atoz\/status-rep-artemisinin-resistance-sep2014.pdf."},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12876"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05753.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-12-118"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit431"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu358"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70252-4"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth904"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.2307\/3280287"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1112037108"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-652-8_6"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014470"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-9-312"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2004.70.119"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-12-320"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.20.010403.104543"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(02)00422-5"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.05.006"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260867"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit415"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064299"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2143"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.04067-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.04067-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T17:59:44Z","timestamp":1645466384000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.04067-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5]]},"references-count":26,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1128\/AAC.04067-14"],"URL":"https:\/\/doi.org\/10.1128\/aac.04067-14","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5]]},"assertion":[{"value":"2014-08-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-04-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}