The susceptibility of Candida albicans strains to selected anticancer drugs and flucytosine, relevance of the presence of self-splicing intron in 25S rDNA

Background: The presence of intron 25S allows to divide the Candida albicans species into three subclasses (A, B, C). Intronless and intron harboring strains were reported to have different susceptibility to some drugs, for example to flucytosine and bleomycin.

Objectives: In this paper we tested the activity of selected antineoplastic agents, bleomycin, mitomycin C, dactinomycin and fluorouracil as well as antifungal drug flucytosine against 49 C. albicans isolates. Twenty-four strains used in this work contained intron, whereas twenty-five were intronless.

Methods: The minimal inhibitory concentrations were determined by the standard microdilution method according to EUCAST.

Results: All of the tested agents showed antifungal activity. Bleomycin was the strongest with an average minimal inhibitory concentration [MIC] of 15.5mg/L (range: 2-32), while the highest MIC was found for dactinomycin: 172.14mg/L (range: 128-256). Intron harboring strains seem to be more susceptible to bleomycin and flucytosine; however, differences were not statistically significant. The only two strains with elevated MICs for flucytosine were intronless. In contrast, the MIC of 5-fluorouracil was more than two times lower in intron harbouring strains comparing to intronless strains (P-value=0.0124). We found that the addition of folinate significantly increased the susceptibility of intronless strains to fluorouracil. MIC of fluorouracil decreased in this group from 58.24 (range: 16-256) to 16,78mg/L (2-64) after the supplementation of folinate.

Conclusion: The antifungal potential of tested substances, especially the simultaneous action of fluorouracil and folinate (combination used in oncology), is encouraging further research.