{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:15:18Z","timestamp":1791296118200,"version":"4.1.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"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":[[2014,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Artemisinin (ART)-based combination therapy (ACT) is used as the first-line treatment of uncomplicated falciparum malaria worldwide. However, despite high potency and rapid action, there is a high rate of recrudescence associated with ART monotherapy or ACT long before the recent emergence of ART resistance. ART-induced ring-stage dormancy and recovery have been implicated as possible causes of recrudescence; however, little is known about the characteristics of dormant parasites, including whether dormant parasites are metabolically active. We investigated the transcription of 12 genes encoding key enzymes in various metabolic pathways in\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            during dihydroartemisinin (DHA)-induced dormancy and recovery. Transcription analysis showed an immediate downregulation for 10 genes following exposure to DHA but continued transcription of 2 genes encoding apicoplast and mitochondrial proteins. Transcription of several additional genes encoding apicoplast and mitochondrial proteins, particularly of genes encoding enzymes in pyruvate metabolism and fatty acid synthesis pathways, was also maintained. Additions of inhibitors for biotin acetyl-coenzyme A (CoA) carboxylase and enoyl-acyl carrier reductase of the fatty acid synthesis pathways delayed the recovery of dormant parasites by 6 and 4 days, respectively, following DHA treatment. Our results demonstrate that most metabolic pathways are downregulated in DHA-induced dormant parasites. In contrast, fatty acid and pyruvate metabolic pathways remain active. These findings highlight new targets to interrupt recovery of parasites from ART-induced dormancy and to reduce the rate of recrudescence following ART treatment.\n          <\/jats:p>","DOI":"10.1128\/aac.02647-14","type":"journal-article","created":{"date-parts":[[2014,6,10]],"date-time":"2014-06-10T07:42:17Z","timestamp":1402386137000},"page":"4773-4781","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":84,"title":["Fatty Acid Synthesis and Pyruvate Metabolism Pathways Remain Active in Dihydroartemisinin-Induced Dormant Ring Stages of Plasmodium falciparum"],"prefix":"10.1128","volume":"58","author":[{"given":"Nanhua","family":"Chen","sequence":"first","affiliation":[{"name":"Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis N.","family":"LaCrue","sequence":"additional","affiliation":[{"name":"Department of Global Health, University of South Florida, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franka","family":"Teuscher","sequence":"additional","affiliation":[{"name":"Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia"},{"name":"Malaria Drug Resistance and Chemotherapy, Queensland Institute of Medical Research, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman C.","family":"Waters","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Gatton","sequence":"additional","affiliation":[{"name":"Malaria Drug Resistance and Chemotherapy, Queensland Institute of Medical Research, Brisbane, Australia"},{"name":"School of Public Health &amp; Social Work, Queensland University of Technology, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis E.","family":"Kyle","sequence":"additional","affiliation":[{"name":"Department of Global Health, University of South Florida, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Australia"},{"name":"Malaria Drug Resistance and Chemotherapy, Queensland Institute of Medical Research, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Report of a WHO technical consultation","author":"WHO","year":"2001","unstructured":"WHO. 2001. Antimalarial drug combination therapy. Report of a WHO technical consultation. World Health Organization, Geneva, Switzerland."},{"key":"e_1_3_2_3_2","volume-title":"World malaria report: 2010","author":"WHO","year":"2011","unstructured":"WHO. 2011. World malaria report: 2010. World Health Organization, Geneva, Switzerland."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.60.2.301-315.1996"},{"key":"e_1_3_2_5_2","article-title":"Artemisinin derivatives for treating uncomplicated malaria","volume":"2","author":"McIntosh HM","year":"2000","unstructured":"McIntoshHMOlliaroP. 2000. Artemisinin derivatives for treating uncomplicated malaria. Cochrane Database Syst. Rev. 2:CD000256.","journal-title":"Cochrane Database Syst. Rev."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2001.65.690"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/656476"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05540-11"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-10-56"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026689"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05456-11"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01636-09"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.2174\/13895575113139990060"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.781840"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.2307\/3280287"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.16.6.710"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00808-06"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkj517"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.091208.073424"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro843"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.05.009"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.11.097"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2007-8-7-r134"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03570.x"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1086\/511436"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022593"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.23.13387"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20050609"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/28970"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.46.30316"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/84612"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(01)00111-4"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.11.001"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.21.12352"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.8.1794"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01270.x"},{"key":"e_1_3_2_37_2","first-page":"237","article-title":"Lipids and the malarial parasite","volume":"55","author":"Holz GG","year":"1977","unstructured":"HolzGGJr. 1977. Lipids and the malarial parasite. Bull. World Health Organ. 55:237\u2013248.","journal-title":"Bull. World Health Organ."},{"key":"e_1_3_2_38_2","first-page":"531","article-title":"Biosynthesis and dynamics of lipids in Plasmodium-infected mature mammalian erythrocytes","volume":"16","author":"Vial HJ","year":"1990","unstructured":"VialHJAncelinMLPhilippotJRThuetMJ. 1990. Biosynthesis and dynamics of lipids in Plasmodium-infected mature mammalian erythrocytes. Blood Cells 16:531\u2013555.","journal-title":"Blood Cells"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05592.x"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06311"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2009.01657.x"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00144-08"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1211037"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2012.01.001"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02647-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.02647-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:52:26Z","timestamp":1645483946000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.02647-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8]]},"references-count":43,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2014,8]]}},"alternative-id":["10.1128\/AAC.02647-14"],"URL":"https:\/\/doi.org\/10.1128\/aac.02647-14","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8]]},"assertion":[{"value":"2014-02-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-06-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-07-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}