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physiological function
integration of a single copy of the yeast fumarate-dependent dihydroorotate dehydrogenase gene yDHODH into the genomes of strains D10attB, 3D7attB, Dd2attB, and HB3attB of Plasmodium falciparum. The yeast gene is equally expressed in all of the transgenic lines. All four yeast dihydroorotate dehydrogenase transgenic lines show strong resistance to atovaquone in standard short-term growth inhibition assays. During longer term growth with atovaquone, D10attB-yDHODH and 3D7attB-yDHODH parasites remain fully resistant, but Dd2attB-yDHODH and HB3attB-yDHODH parasites lose their tolerance to the drug after 3 to 4 days of exposure. No differences are found in growth responses among all of these strains to the Plasmodium-specific DHODH inhibitor DSM1 in either short- or long-term exposures. The ubiquinone analog decylubiquinone substantially reverses the atovaquone inhibition of Dd2attB-yDHODH and HB3attByDHODH transgenic parasites during extended growth
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