{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T18:17:48Z","timestamp":1772216268556,"version":"3.50.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T00:00:00Z","timestamp":1707436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/50026\/2020, PTDC\/SAU-PAR\/2766\/2021, 2022.12892.BD"],"award-info":[{"award-number":["UIDB\/50026\/2020, PTDC\/SAU-PAR\/2766\/2021, 2022.12892.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Malaria parasites increasingly develop resistance to all drugs available in the market, hampering the goal of reducing malaria burden.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Herein, we evaluated the impact of a single-nucleotide variant, E738K, present in the 26S proteasome regulatory subunit <jats:italic>rpn2<\/jats:italic> gene, identified in <jats:italic>Plasmodium chabaudi<\/jats:italic> resistant parasites. Plasmids carrying a functional <jats:italic>rpn2<\/jats:italic> interspecies chimeric gene with 5\u2019 recombination region from <jats:italic>P. falciparum<\/jats:italic> and 3\u2019 from <jats:italic>P. chabaudi<\/jats:italic> were constructed and transfected into Dd2 <jats:italic>P. falciparum<\/jats:italic> parasites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>The 738K variant parasite line presented increased parasite survival when subjected to dihydroartemisinin (DHA), as well as increased chymotrypsin-like activity and decreased accumulation of polyubiquitinated proteins. We thus conclude that the ubiquitin-proteasome pathway, including the 738K variant, play an important role in parasite response to DHA, being the first report of a mutation in a potential DHA drug target enhancing parasite survival and contributing to a significant advance in the understanding the biology of artemisinin resistance.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2024.1342856","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T05:00:31Z","timestamp":1707454831000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Mutation in the 26S proteasome regulatory subunit rpn2 gene in Plasmodium falciparum confers resistance to artemisinin"],"prefix":"10.3389","volume":"14","author":[{"given":"Adriana F.","family":"Gon\u00e7alves","sequence":"first","affiliation":[]},{"given":"Ana","family":"Lima-Pinheiro","sequence":"additional","affiliation":[]},{"given":"Miguel","family":"Teixeira","sequence":"additional","affiliation":[]},{"given":"Gustavo Capatti","family":"Cassiano","sequence":"additional","affiliation":[]},{"given":"Pedro","family":"Cravo","sequence":"additional","affiliation":[]},{"given":"Pedro E.","family":"Ferreira","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2024,2,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijpddr.2011.12.001","article-title":"The proteasome of malaria parasites: A multi-stage drug target for chemotherapeutic intervention","volume":"2","author":"Aminake","year":"2012","journal-title":"Int. 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