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 down-regulation 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.