Abstract
Introduction: Usually, for treatment of fungal infections, antifungals such as azoles are used, but one of the biggest problems faced in clinical practice is the emergence of resistance for most of these drugs. Antifungal drugs derived from plants may alleviate this problem. The aims of this study were to analyse the ergosterol and gene expression profiles of ERG genes in Candida albicans treated with carvacrol. Methods: We used carvacrol and conducted a series of follow-up studies to examine the inhibitors of Candida species isolated from immunocompromised patients. Antifungal susceptibility test, time-kill study, ergosterol binding assay and ergosterol content were investigated. Eventually, the expression of ERG3 and ERG11genes was carried out to investigate the inhibitory properties of antifungal activity against Candida albicans using quantitative real time RT-PCR. Results: Carvacrol was able to inhibit Candida species and reduce time-kill kinetic in C. albicans. This phytoconstituent acted by binding to ergosterol in the fungal membrane and caused a reduction of 52% of the ergosterol content compared to the untreated growth control. Finally, carvacrol displayed significant down-regulation of ERG3 and ERG11genes in C. albicans. Conclusion: These results provide proof of concept for the implementation of carvacrol inhibitors of Candida species. In addition, ERG3 and ERG11 genes could be probable target of carvacrol against C. albicans.
Highlights
For treatment of fungal infections, antifungals such as azoles are used, but one of the biggest problems faced in clinical practice is the emergence of resistance for most of these drugs
The results revealed that carvacrol could able to show antimicrobial properties against clinical isolates of Candida species compared to the standard antifungal agent at 30 μg/mL concentration
According to the literature previously demonstrated that carvacrol has been found to be active against C. albicans [12,13,14,15]
Summary
For treatment of fungal infections, antifungals such as azoles are used, but one of the biggest problems faced in clinical practice is the emergence of resistance for most of these drugs. Antifungal susceptibility test, time-kill study, ergosterol binding assay and ergosterol content were investigated. The expression of ERG3 and ERG11genes was carried out to investigate the inhibitory properties of antifungal activity against Candida albicans using quantitative real time RT-PCR. Results: Carvacrol was able to inhibit Candida species and reduce time-kill kinetic in C. albicans. This phytoconstituent acted by binding to ergosterol in the fungal membrane and caused a reduction of 52% of the ergosterol content compared to the untreated growth control. Antifungal agents in the azole class target the fungal cell membrane through inhibition of the enzyme 14α-demethylase, product of the CYP51/ ERG11, block the biosynthesis of ergosterol and lead to defects in cell membrane integrity and cellular integrity [6,7,8]
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