The Role of Curcumin in Inhibiting Growth of Oropharyngeal Isolates of Candida albicans Fluconazole-Resistant Strain from HIV Patients through Decreased Cdr1p Expression

Abstract

Curcumin is an agent affecting epigenetic factors and the expression of drug efflux transporters such as Cdr1p. Drug efflux transporters are also affected by the epigenetic factor HAT (Histone Acetyl Transferase). HAT-Rtt109 is specific to the fungal kingdom and related to resistance to antifungal agents. Strains of the pathogenic yeast Candida albicans were isolated from AIDS patients with oropharyngeal candidiasis and assigned to control and treatment groups (fluconazole, curcumin and the combination of fluconazole + curcumin). The minimum inhibitory concentration (MIC) for C. albicans resistant strains were determined using tube dilution test in accordance with CLSI micro dilution method, followed by SDS-PAGE. Yeast DNA isolation was performed using DNA isolation kit followed by bisulfate treatment, PCR, and sequencing of Rtt109. The most significant decrease in C. albicans growth occurred on growth media treated with the combination of fluconazole and curcumin. The MIC of the combination group was lower compared to the fluconazole-only or curcuminonly groups. Protein analysis showed that Cdr1p expression for the curcumin and combination groups was decreased compared to the control and fluconazole groups. There was a similar expression of HAT-Rtt109 among four groups. Based on the alignment of Rtt109 sequences, it shows that there was similar methylation among the four groups. The synergy of curcumin and fluconazole to helped in fluconazole resistance was likely through inhibition of Cdr1p expression, but not HAT-Rtt109 or Rtt109 methylation.