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Mutations in the <jats:italic>kelch13<\/jats:italic> (<jats:italic>k13<\/jats:italic>) gene (for example, those resulting in the Cys580Tyr [C580Y] variant) were identified as genetic markers for ART-resistant parasites, which suggests they are associated with resistance mechanisms. However, not all resistant parasites contain a <jats:italic>k13<\/jats:italic> mutation, and clearly greater understanding of resistance mechanisms is required. A genome-wide association study (GWAS) found single nucleotide polymorphisms associated with ART-resistance in <jats:italic>fd<\/jats:italic> (ferredoxin), <jats:italic>arps10<\/jats:italic> (apicoplast ribosomal protein S10), <jats:italic>mdr2<\/jats:italic> (multidrug resistance protein 2), and <jats:italic>crt<\/jats:italic> (chloroquine resistance transporter), in addition to <jats:italic>k13<\/jats:italic> gene mutations, suggesting that these alleles contribute to the resistance phenotype. The importance of the FD and ARPS10 variants in ART resistance was then studied since both proteins likely function in the apicoplast, which is a location distinct from that of K13.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The reported mutations were introduced, together with a mutation to produce the <jats:italic>k13<\/jats:italic>-C580Y variant into the ART-sensitive 3D7 parasite line and the effect on ART-susceptibility using the 0\u22123\u00a0h ring survival assay (RSA<jats:sub>0\u22123\u00a0h<\/jats:sub>) was investigated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results and conclusion<\/jats:title>\n                <jats:p>Introducing both <jats:italic>fd<\/jats:italic>-D193Y and <jats:italic>arps10<\/jats:italic>-V127M into a <jats:italic>k13<\/jats:italic>-C580Y-containing parasite, but not a wild-type <jats:italic>k13<\/jats:italic> parasite, increased survival of the parasite in the RSA<jats:sub>0\u22123\u00a0h<\/jats:sub>. The results suggest epistasis of <jats:italic>arps10<\/jats:italic> and <jats:italic>k13<\/jats:italic>, with <jats:italic>arps10<\/jats:italic>-V127M a modifier of ART susceptibility in different <jats:italic>k13<\/jats:italic> allele backgrounds.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12936-022-04330-3","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T15:22:46Z","timestamp":1666884166000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Apicoplast ribosomal protein S10-V127M enhances artemisinin resistance of a Kelch13 transgenic Plasmodium falciparum"],"prefix":"10.1186","volume":"21","author":[{"given":"Tanyaluck","family":"Kampoun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somdet","family":"Srichairatanakool","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parichat","family":"Prommana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith L.","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Knuepfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony A.","family":"Holder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chairat","family":"Uthaipibull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,27]]},"reference":[{"key":"4330_CR1","doi-asserted-by":"publisher","unstructured":"Fairhurst RM, Dondorp AM. 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