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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2018,12,11]]},"abstract":"<jats:p>\n                    Drug resistance is an obstacle to global malaria control, as evidenced by the recent emergence and rapid spread of delayed artemisinin (ART) clearance by mutant forms of the\n                    <jats:italic>Pf<\/jats:italic>\n                    Kelch13 protein in Southeast Asia. Identifying genetic determinants of ART resistance in African-derived parasites is important for surveillance and for understanding the mechanism of resistance. In this study, we carried out long-term in vitro selection of two recently isolated West African parasites (from Pikine and Thi\u00e8s, Senegal) with increasing concentrations of dihydroartemisinin (DHA), the biologically active form of ART, over a 4-y period. We isolated two parasite clones, one from each original isolate, that exhibited enhanced survival to DHA in the ring-stage survival assay. Whole-genome sequence analysis identified 10 mutations in seven different genes. We chose to focus on the gene encoding\n                    <jats:italic>Pf<\/jats:italic>\n                    Coronin, a member of the WD40-propeller domain protein family, because mutations in this gene occurred in both independent selections, and the protein shares the \u03b2-propeller motif with\n                    <jats:italic>Pf<\/jats:italic>\n                    Kelch13 protein. For functional validation, when\n                    <jats:italic>pfcoronin<\/jats:italic>\n                    mutations were introduced into the parental parasites by CRISPR\/Cas9-mediated gene editing, these mutations were sufficient to reduce ART susceptibility in the parental lines. The discovery of a second gene for ART resistance may yield insights into the molecular mechanisms of resistance. It also suggests that\n                    <jats:italic>pfcoronin<\/jats:italic>\n                    mutants could emerge as a non\n                    <jats:italic>kelch13<\/jats:italic>\n                    type of resistance to ART in natural settings.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1812317115","type":"journal-article","created":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T14:55:32Z","timestamp":1542034532000},"page":"12799-12804","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":174,"title":["Mutations in\n                    <i>Plasmodium falciparum<\/i>\n                    actin-binding protein coronin confer reduced artemisinin susceptibility"],"prefix":"10.1073","volume":"115","author":[{"given":"Allison R.","family":"Demas","sequence":"first","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aabha I.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. 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Chan School of Public Health, Boston, MA 02115;"},{"name":"Infectious Disease and Microbiome Program, Broad Institute, Cambridge, MA 02142;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah K.","family":"Volkman","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115;"},{"name":"Infectious Disease and Microbiome Program, Broad Institute, Cambridge, MA 02142;"},{"name":"School of Nursing and Health Sciences, Simmons College, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Hartl","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115;"},{"name":"Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-4455","authenticated-orcid":false,"given":"Dyann F.","family":"Wirth","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115;"},{"name":"Infectious Disease and Microbiome Program, Broad Institute, Cambridge, MA 02142;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2018,11,12]]},"reference":[{"key":"e_1_3_4_1_2","unstructured":"; World Health Organization World Malaria Report 2017 (World Health Organization Geneva). 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