{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:01:05Z","timestamp":1792425665612,"version":"4.5.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI041930"],"award-info":[{"award-number":["AI041930"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Dihydroorotate dehydrogenase (DHODH) mediates the fourth step of\n            <jats:italic>de novo<\/jats:italic>\n            pyrimidine biosynthesis and is a proven drug target for inducing immunosuppression in therapy of human disease as well as a rapidly emerging drug target for treatment of malaria. In\n            <jats:named-content content-type=\"genus-species\">Toxoplasma gondii<\/jats:named-content>\n            , disruption of the first, fifth, or sixth step of\n            <jats:italic>de novo<\/jats:italic>\n            pyrimidine biosynthesis induced uracil auxotrophy. However, previous attempts to generate uracil auxotrophy by genetically deleting the mitochondrion-associated DHODH of\n            <jats:named-content content-type=\"genus-species\">T. gondii<\/jats:named-content>\n            (\n            <jats:italic>Tg<\/jats:italic>\n            DHODH) failed. To further address the essentiality of\n            <jats:italic>Tg<\/jats:italic>\n            DHODH, mutant gene alleles deficient in\n            <jats:italic>Tg<\/jats:italic>\n            DHODH activity were designed to ablate the enzyme activity. Replacement of the endogenous\n            <jats:italic>DHODH<\/jats:italic>\n            gene with catalytically deficient\n            <jats:italic>DHODH<\/jats:italic>\n            gene alleles induced uracil auxotrophy. Catalytically deficient\n            <jats:italic>Tg<\/jats:italic>\n            DHODH localized to the mitochondria, and parasites retained mitochondrial membrane potential. These results show that\n            <jats:italic>Tg<\/jats:italic>\n            DHODH is essential for the synthesis of pyrimidines and suggest that\n            <jats:italic>Tg<\/jats:italic>\n            DHODH is required for a second essential function independent of its role in pyrimidine biosynthesis.\n          <\/jats:p>","DOI":"10.1128\/iai.00187-16","type":"journal-article","created":{"date-parts":[[2016,8,2]],"date-time":"2016-08-02T03:05:13Z","timestamp":1470107113000},"page":"2974-2981","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":34,"title":["Pyrimidine Pathway-Dependent and -Independent Functions of the Toxoplasma gondii Mitochondrial Dihydroorotate Dehydrogenase"],"prefix":"10.1128","volume":"84","author":[{"given":"Miryam Andrea","family":"Hortua Triana","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Cajiao Herrera","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biol\u00f3gicas, Universidad de los Andes, Bogot\u00e1, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara H.","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Biol\u00f3gicas, Universidad de los Andes, Bogot\u00e1, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Bzik","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"1","volume-title":"Toxoplasma gondii: the model apicomplexan parasite: perspectives and methods","author":"Dubey JP","year":"2007","unstructured":"Dubey JP. 2007. The history and life cycle of Toxoplasma gondii, p 1\u201318. In Weiss LM, Kim K (ed), Toxoplasma gondii: the model apicomplexan parasite: perspectives and methods. 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