Sensitivity and resistance of pathogenic yeasts to 5-fluoropyrimidines. II.--Mechanisms of resistance to 5-fluorocytosine (5-FC) and 5-fluorouracil (5-FU) (author's transl).
Incorporation of labelled 14C-pyrimidines and 5-fluoropyrimidines (5-FC and 5-FU) in four different phenotypes of wild strains of Candida isolated from man showed comparable results to those obtained by the minimal inhibition concentration (MIC) test. Kinetics studies demonstrated significant rates of incorporation after 24 hours of culture in each case. It was also possible to infer the biochemical mechanisms of resistance to 5-FC, namely a defect in UMP pyrophosphorylase, cytosine deaminase and 5-FU permease in the ease of the following phenotypes: 5-FCR 5-FUR, 5-FCR 5-FUS and 5-FCS 5-FUR (R = resistant; S = sensitive). In this study, the permeation process was approached by a consumption assay which determined the rate of labelled substrates into the medium before and after 24 hours of culture. Thus, it was found that the consumption levels of the phenotype 5-FCS 5-FUS were very high, while those of the phenotype 5-FCR 5-FUR were minimal. The 5-FCS 5-FU5 phenotype had no detectable consumption of 5-FU. With regard to the 5-FC5 5-FUS phenotype, it seems that the non-incorporation of 5-FC into the RNAs after the consumption by the yeasts has a feed back effect on the permeation process.
D002175:Candida / Q000187:drug effects* / Q000378:metabolism; D003596:Cytosine / Q000031:analogs & derivatives*; D004352:Drug Resistance, Microbial; D005437:Flucytosine / Q000378:metabolism / Q000494:pharmacology*; D005472:Fluorouracil / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D010641:Phenotype; D013045:Species Specificity
D003596:Cytosine; D005437:Flucytosine; D005472:Fluorouracil
Sensibilité et résistance des levures pathogènes aux 5-fluoropyrimidines. II.--Etude des mécanismes de résistance a la 5-fluorocytosine (5-FC) et au 5-fluorouracile (5-FU)