Abstract
The mechanism of 5-fluorocytosine (5-FC) resistance was studied in highly resistant mutants isolated from Saccharomyces cerevisiae ATCC 9763. The development of resistance to 5-FC in these strains was caused by the obstruction of further enzymatic conversion of 5-fluorouracil (5-FU), produced by deamination of 5-FC in the cells, due to the lack of UMP pyrophosphorylase. Consequently, 5-FC was not incorporated into RNA, the most probable site of the antifungal activity of 5-FC. The 5-FU thus formed in the cells was excreted rapidly into the medium, thereby the resistant strains effectively remove toxic effects, if any, of the derived 5-FU from the cells.
The mechanism for the simultaneous acquisition of the cross-resistance to 5-FU was also elucidated by the differences in the abilities to incorporate 5-FU by the sensitive and resistant strains.
The similar mechanism of 5-FC resistance was also predicted in the case of Fonsecaea pedrosoi, a clinical isolate.
