Fenpropimorph affects uptake of uracil and cytosine in Saccharomyces cerevisiae

Fenpropimorph was shown to inhibit the accumulation of the pyrimidine bases uracil and cytosine from the growth media in Saccharomyces cerevisiae. Uracil prototrophs of S. cerevisiae were more resistant to the growth-inhibitory effects of fenpropimorph than were uracil auxotrophs. High concentrations of uracil rescued fenpropimorph-treated uracil auxotrophs, and cytosine, which is accumulated by a separate mechanism, could also support growth of treated uracil auxotrophs. Fenpropimorph caused a significant decrease in the uptake of radiolabeled uracil, which was not due to accumulation of ergosta-8,14-dienol (ignosterol) in the treated cultures. Radiolabeled cytosine uptake was unaffected by drug treatment in a wild-type strain but was inhibited in a sterol mutant, in which ergosterol was absent from the cell. The role of fenpropimorph in causing membrane dysfunction through a mechanism other than altered sterol metabolism is discussed.