Mechanisms of action of 5-fluorocytosine.
5-Fluorouracil and 5-fluorodeoxyuridine monophosphate levels were estimated in 75 isolates of Candida albicans to determine whether 5-fluorocytosine susceptibility could be ideally correlated with the intrafungal formation of both 5-fluorodeoxyuridine monophosphate and 5-fluorouridine triphosphate or a reciprocal formation of the two metabolites to prove the mechanism of 5-fluorocytosine activity. Using the results of four in vitro susceptibility tests, we separated isolates of C. albicans into susceptibility groups. For most strains, there was a positive correlation between the degree of 5-fluorocytosine susceptibility and the inhibition of biosynthesis of both RNA and DNA, incorporation of 5-fluorouracil into RNA, inhibition of ribosomal protein synthesis, and levels of 5-fluorodeoxyuridine monophosphate. However, in some strains with a similar degree of 5-fluorocytosine resistance, either reduced incorporation of 5-fluorouracil or reduced 5-fluorodeoxyuridine monophosphate levels occurred, suggesting that these two mechanisms are not necessarily linked to each other and that both may be responsible for 5-fluorocytosine activity.
D002176:Candida albicans / Q000187:drug effects / Q000378:metabolism; D003596:Cytosine / Q000031:analogs & derivatives*; D004271:DNA, Fungal / Q000096:biosynthesis; D005437:Flucytosine / Q000494:pharmacology*; D012331:RNA, Fungal / Q000096:biosynthesis; D012269:Ribosomal Proteins / Q000096:biosynthesis; D013940:Thymidylate Synthase / Q000032:analysis; D014544:Uridine Triphosphate / Q000031:analogs & derivatives / Q000032:analysis
D004271:DNA, Fungal; D012331:RNA, Fungal; D012269:Ribosomal Proteins; C025635:5-fluorouridine 5'-triphosphate; D003596:Cytosine; D005437:Flucytosine; D013940:Thymidylate Synthase; D014544:Uridine Triphosphate