Functional Complementation of Human cDNAs for P-Gp Variants in a Drug-Sensitive Yeast Strain

<div><p>(A) Differences in drug sensitivity of yeast strains. Yeast strains tested included mutants in which combinations of three major endogenous multidrug transporter genes, <i>PDR5</i>, <i>SNQ2</i>, and <i>YOR1</i>, were deleted. Cultures from each strain were adjusted to the same cell concentration and serially diluted 5-fold. The genotypes of the strains tested are shown in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0030039#pgen-0030039-st001" target="_blank">Table S1</a>. The <i>pdr5 snq2 yor1</i> triple mutant was consistently the most sensitive strain to daunorubicin and doxorubicin.</p><p>(B) Restoration of drug resistance in the hyper-sensitized yeast strain by P-gp variants. Cultures from each strain were adjusted to the same cell concentration and serially diluted 5-fold. Variants restored drug resistance of the hyper-sensitized yeast strain to varying degrees. The strains tested are <i>pdr5 snq2 yor1</i> with plasmids carrying the indicated variants (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0030039#pgen-0030039-st001" target="_blank">Table S1</a>). A frame-shifted P-gp was used as a negative control.</p>