{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T07:42:05Z","timestamp":1791099725584,"version":"4.1.0"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2010,6,1]],"date-time":"2010-06-01T00:00:00Z","timestamp":1275350400000},"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":[[2010,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Artemisinin and its derivatives are the most rapidly acting and efficacious antimalarial drugs currently available. Although resistance to these drugs has not been documented, there is growing concern about the potential for resistance to develop. In this paper we report the selection of parasite resistance to artelinic acid (AL) and artemisinin (QHS)<jats:italic>in vitro<\/jats:italic>and the molecular changes that occurred during the selection. Exposure of three<jats:italic>Plasmodium falciparum<\/jats:italic>lines (W2, D6, and TM91C235) to AL resulted in decreases in parasite susceptibilities to AL and QHS, as well as to mefloquine, quinine, halofantrine, and lumefantrine. The changes in parasite susceptibility were accompanied by increases in the copy number, mRNA expression, and protein expression of the<jats:italic>pfmdr1<\/jats:italic>gene in the resistant progenies of W2 and TM91C235 parasites but not in those of D6 parasites. No changes were detected in the coding sequences of the<jats:italic>pfmdr1<\/jats:italic>,<jats:italic>pfcrt<\/jats:italic>,<jats:italic>pfatp6<\/jats:italic>,<jats:italic>pftctp<\/jats:italic>, and<jats:italic>pfubcth<\/jats:italic>genes or in the expression levels of<jats:italic>pfatp6<\/jats:italic>and<jats:italic>pftctp<\/jats:italic>. Our data demonstrate that<jats:italic>P. falciparum<\/jats:italic>lines have the capacity to develop resistance to artemisinin derivatives<jats:italic>in vitro<\/jats:italic>and that this resistance is achieved by multiple mechanisms, to include amplification and increased expression of<jats:italic>pfmdr1<\/jats:italic>, a mechanism that also confers resistance to mefloquine. This observation is of practical importance, because artemisinin drugs are often used in combination with mefloquine for the treatment of malaria.<\/jats:p>","DOI":"10.1128\/aac.00947-09","type":"journal-article","created":{"date-parts":[[2010,3,30]],"date-time":"2010-03-30T03:55:06Z","timestamp":1269921306000},"page":"2455-2464","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":105,"title":["Role of<i>pfmdr1<\/i>Amplification and Expression in Induction of Resistance to Artemisinin Derivatives in<i>Plasmodium falciparum<\/i>"],"prefix":"10.1128","volume":"54","author":[{"given":"Marina","family":"Chavchich","sequence":"first","affiliation":[{"name":"Australian Army Malaria Institute, Weary Dunlop Drive, Gallipoli Barracks, Enoggera, Q4051"},{"name":"Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Herston, Q4029, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Gerena","sequence":"additional","affiliation":[{"name":"Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Peters","sequence":"additional","affiliation":[{"name":"Australian Army Malaria Institute, Weary Dunlop Drive, Gallipoli Barracks, Enoggera, Q4051"},{"name":"Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Herston, Q4029, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanhua","family":"Chen","sequence":"additional","affiliation":[{"name":"Australian Army Malaria Institute, Weary Dunlop Drive, Gallipoli Barracks, Enoggera, Q4051"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Cheng","sequence":"additional","affiliation":[{"name":"Australian Army Malaria Institute, Weary Dunlop Drive, Gallipoli Barracks, Enoggera, Q4051"},{"name":"Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Herston, Q4029, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis E.","family":"Kyle","sequence":"additional","affiliation":[{"name":"Australian Army Malaria Institute, Weary Dunlop Drive, Gallipoli Barracks, Enoggera, Q4051"},{"name":"Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910"},{"name":"Department of Global Health, College of Public Health, University of South Florida, 3720 Spectrum Blvd., Tampa, Florida 33612"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.2.480-489.2006"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2007.76.641"},{"key":"e_1_3_2_4_2","unstructured":"User bulletin #2. 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