Abstract
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.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Block E. R., Jennings A. E., Bennett J. E. 5-fluorocytosine resistance in Cryptococcus neoformans. Antimicrob Agents Chemother. 1973 Jun;3(6):649–656. doi: 10.1128/aac.3.6.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Diasio R. B., Bennett J. E., Myers C. E. Mode of action of 5-fluorocytosine. Biochem Pharmacol. 1978 Mar 1;27(5):703–707. doi: 10.1016/0006-2952(78)90507-5. [DOI] [PubMed] [Google Scholar]
- Galgiani J. N., Stevens D. A. Antimicrobial susceptibility testing of yeasts: a turbidimetric technique independent of inoculum size. Antimicrob Agents Chemother. 1976 Oct;10(4):721–728. doi: 10.1128/aac.10.4.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HARTMANN K. U., HEIDELBERGER C. Studies on fluorinated pyrimidines. XIII. Inhibition of thymidylate synthetase. J Biol Chem. 1961 Nov;236:3006–3013. [PubMed] [Google Scholar]
- Polak A. 5-Fluorocytosine--current status with special references to mode of action and drug resistance. Contrib Microbiol Immunol. 1977;4:158–167. [PubMed] [Google Scholar]
- Polak A., Scholer H. J. Fungistatic activity, uptake and incorporation of 5-fluorocytosine in Candida albicans, as influenced by pyrimidines and purines. I. Reversal experiments. Pathol Microbiol (Basel) 1973;39(2):148–159. doi: 10.1159/000162642. [DOI] [PubMed] [Google Scholar]
- Polak A., Scholer H. J. Fungistatic activity, uptake and incorporation of 5-fluorocytosine in Candida albicans, as influenced by pyrimidines and purines. II. Studies on distribution and incorporation. Pathol Microbiol (Basel) 1973;39(5):334–337. [PubMed] [Google Scholar]
- Polak A., Scholer H. J. Mode of action of 5-fluorocytosine and mechanisms of resistance. Chemotherapy. 1975;21(3-4):113–130. doi: 10.1159/000221854. [DOI] [PubMed] [Google Scholar]
- Polak A., Wain W. H. The effect of 5-fluorocytosine on the blastospores and hyphae of Candida albicans. J Med Microbiol. 1979 Feb;12(1):83–97. doi: 10.1099/00222615-12-1-83. [DOI] [PubMed] [Google Scholar]
- Polak A., Wain W. H. The influence of 5-fluorocytosine on nucleic acid synthesis in Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus. Chemotherapy. 1977;23(4):243–259. doi: 10.1159/000221992. [DOI] [PubMed] [Google Scholar]
- Stiller R. L., Bennett J. E., Scholer H. J., Wall M., Polak A., Stevens D. A. Susceptibility to 5-fluorocytosine and prevalence of serotype in 402 Candida albicans isolates from the United States. Antimicrob Agents Chemother. 1982 Sep;22(3):482–487. doi: 10.1128/aac.22.3.482. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wain W. H., Polak A. The effect of 5-fluorocytosine on the synthesis of 80S ribosomes by pathogenic fungi. Sabouraudia. 1981 Sep;19(3):187–197. doi: 10.1080/00362178185380301. [DOI] [PubMed] [Google Scholar]
- Wain W. H., Price M. F., Brayton A. R., Cawson R. A. Macromolecular syntheses during the cell cycles of yeast and hyphal phases of Candida albicans. J Gen Microbiol. 1976 Dec;97(2):211–217. doi: 10.1099/00221287-97-2-211. [DOI] [PubMed] [Google Scholar]