{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:16:58Z","timestamp":1793146618007,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1009266","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,1,8]],"date-time":"2021-01-08T00:00:00Z","timestamp":1610064000000}}],"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T00:00:00Z","timestamp":1609113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI099105"],"award-info":[{"award-number":["R01AI099105"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI099105"],"award-info":[{"award-number":["R01AI099105"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1156051"],"award-info":[{"award-number":["OPP1156051"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Harvard Defeating Malaria Initiative"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Malaria continues to impose a significant health burden in the continent of Africa with 213 million cases in 2018 alone, representing 93% of cases worldwide. Because of high transmission of malaria within the continent, the selection pressures to develop drug resistance in African parasites are distinct compared to the rest of the world. In light of the spread of resistance to artemisinin conferred by the C580Y mutation in the\n                    <jats:italic>Pf<\/jats:italic>\n                    Kelch13 propeller domain in Southeast Asia, and its independent emergence in South America, it is important to study genetic determinants of resistance in the African context using African parasites. Through\n                    <jats:italic>in vitro<\/jats:italic>\n                    evolution of Senegalese parasites, we had previously generated the artemisinin-resistant parasites Pikine_R and Thi\u00e8s_R and established\n                    <jats:italic>pfcoronin<\/jats:italic>\n                    mutations to be sufficient to confer artemisinin resistance in the standard ring-stage survival assay (RSA). In the current study, we used genetic analysis of revertants to demonstrate\n                    <jats:italic>pfcoronin<\/jats:italic>\n                    to be the major driver of elevated RSA in the artemisinin-resistant parasites Pikine_R and Thi\u00e8s_R evolved\n                    <jats:italic>in vitro<\/jats:italic>\n                    . We interrogated the role of a second gene\n                    <jats:italic>PF3D7_1433800<\/jats:italic>\n                    , which also had mutations in both the Pikine_R and Thi\u00e8s_R selected lines, but found no evidence of a contribution to reduced susceptibility in the RSA survival assay. Nevertheless, our genetic analysis demonstrates that parasite genetic background is important in the level of\n                    <jats:italic>pfcoronin<\/jats:italic>\n                    mediated RSA survival, and therefore we cannot rule out a role for PF3D7_1433800 in other genetic backgrounds. Finally, we tested the potential synergy between the mutations of\n                    <jats:italic>pfcoronin<\/jats:italic>\n                    and\n                    <jats:italic>pfkelch13<\/jats:italic>\n                    through the generation of single and double mutants in the Pikine genetic background and found that the contribution of\n                    <jats:italic>pfcoronin<\/jats:italic>\n                    to reduced susceptibility is masked by the presence of\n                    <jats:italic>pfkelch13<\/jats:italic>\n                    . This phenomenon was also observed in the 3D7 background, suggesting that\n                    <jats:italic>pfcoronin<\/jats:italic>\n                    may mediate its effects via the same pathway as\n                    <jats:italic>pfkelch13<\/jats:italic>\n                    . Investigating the biology of proteins containing the beta-propeller domain could further elucidate the different pathways that the parasite could use to attain resistance.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1009266","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T15:52:41Z","timestamp":1609170761000},"page":"e1009266","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":37,"title":["Genetic background and PfKelch13 affect artemisinin susceptibility of PfCoronin mutants in Plasmodium falciparum"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0209-5608","authenticated-orcid":true,"given":"Aabha I.","family":"Sharma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara H.","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9412-9766","authenticated-orcid":true,"given":"Selina","family":"Bopp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah K.","family":"Volkman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0302-306X","authenticated-orcid":true,"given":"Daniel L.","family":"Hartl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-4455","authenticated-orcid":true,"given":"Dyann F.","family":"Wirth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,28]]},"reference":[{"key":"pgen.1009266.ref001","volume-title":"World 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