{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:51:14Z","timestamp":1793393474039,"version":"4.5.0"},"reference-count":23,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 130359"],"award-info":[{"award-number":["MOP 130359"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Dihydroartemisinin-piperaquine (DHA-PPQ), the current frontline artemisinin combination therapy used to treat\n            <jats:named-content content-type=\"genus-species\">Plasmodium falciparum<\/jats:named-content>\n            malaria in multiple Southeast Asian countries, is now increasingly failing in Cambodia, where artemisinin resistance is nearly fixed, which suggests that PPQ resistance has emerged and is spreading rapidly in the Greater Mekong Subregion. Recent reports have shown that amplification of the genes encoding plasmepsins 2 and 3 is a molecular marker of PPQ resistance; however, whether these enzymes play a role in the mechanism of resistance is currently unknown. We show here that inactivating the genes encoding plasmepsin 2 or 3 individually in\n            <jats:named-content content-type=\"genus-species\">P. falciparum<\/jats:named-content>\n            reference strain 3D7 results in hypersusceptibility to PPQ. Interestingly, no significant differences in the susceptibility to other antimalarials were observed, which suggests specific roles of plasmepsins 2 and 3 in PPQ susceptibility. The piperaquine hyper-sensitivity of the plasmepsin-2-and-3-inactivated lines provides direct evidence that these enzymes modulate parasite susceptibility to PPQ in the context of a single copy of\n            <jats:italic>PfMDR1<\/jats:italic>\n            and independent of Kelch13 mutations conferring artemisinin resistance.\n          <\/jats:p>","DOI":"10.1128\/aac.02309-17","type":"journal-article","created":{"date-parts":[[2018,2,13]],"date-time":"2018-02-13T11:33:43Z","timestamp":1518521623000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["Inactivation of Plasmepsins 2 and 3 Sensitizes Plasmodium falciparum to the Antimalarial Drug Piperaquine"],"prefix":"10.1128","volume":"62","author":[{"given":"Angana","family":"Mukherjee","sequence":"first","affiliation":[{"name":"Centre de recherche en infectiologie du CHU de Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada"},{"name":"Harvard T.H. Chan School of Public Health, Boston, Massachussetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Gagnon","sequence":"additional","affiliation":[{"name":"Centre de recherche en infectiologie du CHU de Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dyann F.","family":"Wirth","sequence":"additional","affiliation":[{"name":"Harvard T.H. Chan School of Public Health, Boston, Massachussetts, United States"},{"name":"The Broad Institute of MIT and Harvard, Cambridge, Massachussetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2269-6240","authenticated-orcid":false,"given":"Dave","family":"Richard","sequence":"additional","affiliation":[{"name":"Centre de recherche en infectiologie du CHU de Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec City, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"World Malaria Report","author":"WHO","year":"2016","unstructured":"WHO. 2016. World Malaria Report. 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