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Gene editing technologies have been used to validate the role of several candidate K13 mutations in mediating\n                    <jats:named-content content-type=\"genus-species\">P. falciparum<\/jats:named-content>\n                    artemisinin resistance\n                    <jats:italic>in vitro<\/jats:italic>\n                    under laboratory conditions. Nonetheless, the causal role of these mutations under\n                    <jats:italic>in vivo<\/jats:italic>\n                    conditions has been a matter of debate. Here, we have used CRISPR\/Cas9 gene editing to introduce K13 mutations associated with artemisinin resistance into the related rodent-infecting parasite,\n                    <jats:named-content content-type=\"genus-species\">Plasmodium berghei<\/jats:named-content>\n                    . Phenotyping of these\n                    <jats:named-content content-type=\"genus-species\">P. berghei<\/jats:named-content>\n                    K13 mutant parasites provides evidence of their role in mediating artemisinin resistance\n                    <jats:italic>in vivo<\/jats:italic>\n                    , which supports\n                    <jats:italic>in vitro<\/jats:italic>\n                    artemisinin resistance observations. However, we were unable to introduce some of the\n                    <jats:named-content content-type=\"genus-species\">P. falciparum<\/jats:named-content>\n                    K13 mutations (C580Y and I543T) into the corresponding amino acid residues, while other introduced mutations (M476I and R539T equivalents) carried pronounced fitness costs. Our study provides evidence of a clear causal role of K13 mutations in modulating susceptibility to artemisinins\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    using the well-characterized\n                    <jats:named-content content-type=\"genus-species\">P. berghei<\/jats:named-content>\n                    model. We also show that inhibition of the\n                    <jats:named-content content-type=\"genus-species\">P. berghei<\/jats:named-content>\n                    proteasome offsets parasite resistance to artemisinins in these mutant lines.\n                  <\/jats:p>","DOI":"10.1128\/mbio.02312-20","type":"journal-article","created":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T09:29:54Z","timestamp":1604914194000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Plasmodium berghei K13 Mutations Mediate\n                    <i>In Vivo<\/i>\n                    Artemisinin Resistance That Is Reversed by Proteasome Inhibition"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4734-0518","authenticated-orcid":false,"given":"Nelson V.","family":"Simwela","sequence":"first","affiliation":[{"name":"Institute of Infection, Immunity &amp; Inflammation, Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9519-487X","authenticated-orcid":false,"given":"Barbara H.","family":"Stokes","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Aghabi","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity &amp; Inflammation, Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3753-4412","authenticated-orcid":false,"given":"Matt","family":"Bogyo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"},{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-8938","authenticated-orcid":false,"given":"David A.","family":"Fidock","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8900-2982","authenticated-orcid":false,"given":"Andrew P.","family":"Waters","sequence":"additional","affiliation":[{"name":"Institute of Infection, Immunity &amp; Inflammation, Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1155165"},{"key":"e_1_3_2_3_2","volume-title":"World malaria report","author":"WHO","year":"2019","unstructured":"WHO. 2019. 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