@conference{
author = "Carević, Tamara and Glamočlija, Jasmina and Nikolić, Biljana and Ivanov, Marija and Soković, Marina",
year = "2022",
abstract = "The frequency of resistance to a large number of antimicrobial agents is increasing, so there
is a need to find new ones. A major problem in the treatment of infections caused by Candida
albicans is a highly resistant biofilm, which is a virulence factor of this species. The
mechanisms of action of selected flavonoids (hesperetin, sakuranetin, and taxifolin) on
species of the genus Candida were explored. The strains that were tested were C. albicans
10/15, C. albicans 13/15, C. albicans ATCC 10231, C. albicans 475/15, C. parapsilosis
ATCC 22019, C. tropicalis ATCC 750, C. krusei H1/16, and C. glabrata 4/6/15. The
antimicrobial potential of flavonoids was investigated by the microdilution method.
Determining the ability of these compounds to disrupt virulence factors, in the model of
Candida albicans, is based on monitoring the process of disrupting the formation and
destruction of previously formed biofilm. The cytotoxic effect on selected human cell lines
(lung fibroblasts) was investigated in order to determine whether flavonoids are selectively
toxic to species of the genus Candida, or cause non-selective toxicity in eukaryotic cells. The
laboratory methods used were microdilution method, antibiofilm method (crystal violet assay,
measures biofilm biomass), Congo red binding assay (measures the influence of compounds
on exopolysaccharide, EPS, production in biofilm), MTT cytotoxicity assay. The most
pronounced antifungal potential was observed for sakuranetin with a MIC of 0.041 mg/mL
for C. parapsilosis ATCC 22019 and a MIC of 0.082 mg/mL for the other strains tested. The
antimicrobial potential of hesperetin and taxifolin is the same for all tested strains; MIC value
is 0.165 mg/mL. All substances have been shown to be effective in inhibiting biofilm
formation, but also in destroying it. The antibiofilm effect of sakuranetin applied in
concentration equal to MIC against C. glabrata 4/6/15 and C. krusei H1/16 is over 85%.
These two strains are the most sensitive to the action of sakuranetin. The ability to destroy the
previously formed biofilm was pronounced towards C. albicans 475/15 (52.80%), and
moderate towards C. albicans ATCC 10231 (12.22%). The antibiofilm potential of hesperetin
is high for C. glabrata 4/6/15 (70.4%) and C. parapsilosis ATCC 22019 (62.6%), while for
other strains the percentage of inhibition is less than 50%, and for the formation of biofilm C.
krusei H1/16 hesperetin has no effect at all. The distinct effect of this flavonoid on the
destruction of previously formed biofilm is emphasized, with significant percentages of
destruction, while the percentages of EPS inhibition are low but significant (higher or closer
to the effect of ketoconazole). The most pronounced antibiofilm effect of taxifolin is
exhibited towards C. glabrata 4/6/15 (61.6%), while the percentage of inhibition is not higher
than 50% for other strains, which is generally lower effect than for other tested substances.
The cytotoxicity test indicates the following range of sensitivity of the examined cell line to
flavonoids: sakuranetin>hesperetin>taxifolin. The tested flavonoids have excellent potential
to be part of antifungal therapies, especially hesperetin, which has shown a strong antibiofilm
effect with pronounced selectivity towards pathogen cells.",
publisher = "Novi Sad: Matica srpska",
journal = "Book of abstracts: The 7th international scientific meeting "Mycology, mycotoxicology, and mycoses"; 2022 Jun 2-3; Novi Sad, Serbia",
title = "Mechanisms of action of selected flavonoids towards species of the genus Candida",
pages = "46",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5332"
}