{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:53:09Z","timestamp":1790376789194,"version":"4.1.0"},"reference-count":13,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T00:00:00Z","timestamp":1375315200000},"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":[[2013,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Evidence of artemisinin (ART) resistance in all of the Greater Mekong Region is currently of major concern. Understanding of the mechanisms of resistance developed by\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium<\/jats:named-content>\n            against artemisinin and its derivatives is urgently needed. We here demonstrated that ART was able to alkylate heme in mice infected by the ART-susceptible strain of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium yoelii nigeriensis<\/jats:named-content>\n            , Y-control. After long-term drug pressure, the parasite strain (Y-ART3) was 5-fold less susceptible to ART than Y-control. In the blood of mice infected by Y-ART3, no heme-artemisinin adducts could be detected. After release of ART drug pressure, the parasite strain obtained (Y-REL) regained both drug susceptibility to ART and increased ability to produce covalent heme-artemisinin adducts. The correlation between parasite ART susceptibility and alkylation of heme by the drug confirms that heme or hemozoin metabolism is a key target for efficacy of ART as an antimalarial.\n          <\/jats:p>","DOI":"10.1128\/aac.01064-13","type":"journal-article","created":{"date-parts":[[2013,6,11]],"date-time":"2013-06-11T04:02:11Z","timestamp":1370923331000},"page":"3998-4000","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Correlation between Plasmodium yoelii nigeriensis Susceptibility to Artemisinin and Alkylation of Heme by the Drug"],"prefix":"10.1128","volume":"57","author":[{"given":"Anne","family":"Robert","sequence":"first","affiliation":[{"name":"CNRS, LCC (Laboratoire de Chimie de Coordination) UPR 8241, Toulouse, France"},{"name":"Universit\u00e9 de Toulouse, UPS, INPT, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Claparols","sequence":"additional","affiliation":[{"name":"CNRS, LCC (Laboratoire de Chimie de Coordination) UPR 8241, Toulouse, France"},{"name":"Universit\u00e9 de Toulouse, UPS, INPT, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Witkowski","sequence":"additional","affiliation":[{"name":"CNRS, LCC (Laboratoire de Chimie de Coordination) UPR 8241, Toulouse, France"},{"name":"Universit\u00e9 de Toulouse, UPS, INPT, Toulouse, France"},{"name":"Service de Parasitologie et Mycologie and Facult\u00e9 de M\u00e9decine de Rangueil, Centre Hospitalier Universitaire de Toulouse, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Benoit-Vical","sequence":"additional","affiliation":[{"name":"CNRS, LCC (Laboratoire de Chimie de Coordination) UPR 8241, Toulouse, France"},{"name":"Universit\u00e9 de Toulouse, UPS, INPT, Toulouse, France"},{"name":"Service de Parasitologie et Mycologie and Facult\u00e9 de M\u00e9decine de Rangueil, Centre Hospitalier Universitaire de Toulouse, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"WHO. 13 December 2011. World Malaria Report 2011. World Health Organization Geneva Switzerland. http:\/\/www.who.int\/malaria\/world_malaria_report_2011\/WMR2011_factsheet.pdf."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61963-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-11-424"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01868-12"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar100070k"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3773(20010518)40:10<1954::AID-ANIE1954>3.0.CO;2-9"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1039\/B110817B"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500972102"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00239-07"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032620"},{"key":"e_1_3_2_13_2","volume-title":"Methods in malaria research","author":"Moll K","year":"2008","unstructured":"2008. MollK Ljungstr\u00f6mI PerlmannH ScherfA WahlgrenM (ed), Methods in malaria research, 5th ed. 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