Antifungal Activity of Carvacrol on Ergosterol Synthesis in Multidrug Resistant Candida albicans

Introduction: Greatly increased use of antifungal therapies has resulted in the
development of multidrug resistant. The phenolic compound carvacrol have been
reported to have anti-Candida activity. This work is an attempt to examine effect of
carvacrol on ergosterol synthesis against multidrug resistant Candida albicans.
Methods: This cross-sectional study has been conducted on 30 immune-compromised
patients from vagina, mouth and skin surfaces during 2016-2017. Colonizing clinical
isolates of C. albicans were identified and drug resistant isolates detected using
WHONET software. The susceptibility tests for carvacrol were carried out in terms of
disk diffusion, broth microdilution and time kill assays against multidrug resistant C.
albicans. The ability to change from yeast to hyphal morphology exploited using a light
microscopy. Ergosterol quantification has been investigated by spectrophotometric
analysis. The expression profile of ERG11 gene was studied using quantitative real time
RT-PCR to admit the possibility of further associated ergosterol pathway. Statistical
analysis was performed with SPSS 21.0. Comparisons were performed using one-way
ANOVA, with Tukey’s tests.
Results: Ten colonizing clinical isolates of C. albicans were identified. Multidrug resistant
isolates of C. albicans were detected. Carvacrol was found to have MIC90 of 100-200 μg/ml
for multidrug drug resistant isolates of C. albicans. The time kill curve results show that
carvacrol could significantly inhibit the growth of C. albicans (P≤0.05). In multidrug
resistant C. albicans treated with carvacrol there was a marked reduction of the transition
of yeast cells to hyphal cells. Significant decrease of ergosterol content was noted in
multidrug resistant C. albicans treated with carvacrol. Furthermore, significant downregulation
was observed on ERG11 gene in multidrug resistant C. albicans treated with
carvacrol (P≤0.05).
Conclusion: Carvacrol show strong antifungal activity against multidrug resistant C.
albicans. These results provide proof of concept for the implementation of carvacrol
that may have potential applications in the treatment of drug resistance C. albicans
infections.