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In this study, we demonstrate that inhibition of glutathione biosynthesis in the\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium berghei<\/jats:named-content>\n            ANKA strain through disruption of the \u03b3-glutamylcysteine synthetase (\u03b3-GCS) gene, which encodes the first and rate-limiting enzyme in the glutathione biosynthetic pathway, significantly sensitizes parasites\n            <jats:italic>in vivo<\/jats:italic>\n            to pyrimethamine and sulfadoxine, but not to chloroquine, artesunate, or primaquine, compared with control parasites containing the same pyrimethamine-resistant marker cassette. Treatment of mice infected with an antifolate-resistant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. berghei<\/jats:named-content>\n            control line with a \u03b3-GCS inhibitor, buthionine sulfoximine, could partially abrogate pyrimethamine and sulfadoxine resistance. The role of glutathione in modulating the malaria parasite's response to antifolates suggests that development of specific inhibitors against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium<\/jats:named-content>\n            \u03b3-GCS may offer a new approach to counter\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium<\/jats:named-content>\n            antifolate resistance.\n          <\/jats:p>","DOI":"10.1128\/aac.01836-15","type":"journal-article","created":{"date-parts":[[2016,3,8]],"date-time":"2016-03-08T03:39:18Z","timestamp":1457408358000},"page":"3057-3064","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Inhibition of Glutathione Biosynthesis Sensitizes Plasmodium berghei to Antifolates"],"prefix":"10.1128","volume":"60","author":[{"given":"Warangkhana","family":"Songsungthong","sequence":"first","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pongpisid","family":"Koonyosying","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chairat","family":"Uthaipibull","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumalee","family":"Kamchonwongpaisan","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"World malaria report 2015","author":"WHO","year":"2015","unstructured":"WHO. 2015. 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