Antifungal Activity of the Phenolic Compounds Ellagic Acid (EA) and Caffeic Acid Phenethyl Ester (CAPE) against Drug-Resistant Candida auris

Abstract

Candida auris is an emerging healthcare-associated fungal pathogen that has become a serious global health threat. Current treatment options are limited due to drug resistance. New therapeutic strategies are required to target this organism and its pathogenicity. Plant polyphenols are structurally diverse compounds that present a vast range of biological properties. In the present study, plant-derived molecules ellagic acid (EA) and caffeic acid phenethyl ester (CAPE) were investigated for their antifungal and antivirulence activities against Candida auris. We also tested against C. albicans. The minimum inhibitory concentration (MIC) for EA ranged from 0.125 to 0.25 µg/mL and for CAPE ranged from 1 to 64 µg/mL against drug-resistant C. auris strains. Killing kinetics determined that after 4 h treatment with CAPE, there was a complete reduction of viable C. auris cells compared to fluconazole. Both compounds might act by modifying the fungal cell wall. CAPE significantly reduced the biomass and the metabolic activity of C. auris biofilm and impaired C. auris adhesion to cultured human epithelial cells. Furthermore, both compounds prolonged the survival rate of Galleria mellonella infected by C. auris (p = 0.0088 for EA at 32 mg/kg and p = 0.0028 for CAPE at 4 mg/kg). In addition, EA at 4 μg/mL prolonged the survival of C. albicans-infected Caenorhabditis elegans (p < 0.0001). CAPE was not able to prolong the survival of C. albicans-infected C. elegans. These findings highlight the antifungal and antivirulence effects of EA and CAPE against C. auris, and warrant further investigation as novel antifungal agents against drug-resistant infections.

Antifungal and Anti-Biofilm Effects of Caffeic Acid Phenethyl Ester on Different Candida Species

“…Another study performed by Possamai Rossatto and coworkers showed similar results, where CAPE was also able to inhibit the growth of C. auris with MIC values ranging from 1 to 64 µg/mL. Furthermore, CAPE was able to inhibit the biofilm formation and phospholipase production of C. auris [ 30 ]. Our findings also showed the ability of CAPE to enter the cells of Candida spp rapidly.…”

Identification and functional characterization of ORF19.5274, a novel gene involved in both azoles susceptibility and hypha development in Candida albicans

“…The biofilm extracellular matrix is a second major contributor to antifungal drug resistance in C. albicans biofilms. The matrix acts as both a physical barrier to drug penetration and as a stabilizer of the overall architecture of the biofilms ( Nett et al, 2007 ; Nobile and Johnson, 2015 ), isolating antifungal molecules and preventing them from penetrating deeper into the biofilm ( Pierce et al, 2013 ; Possamai Rossatto et al, 2021 ). A third important resistance property is the biofilm-regulated efflux pumps.…”

Special Issue: Alternative Therapeutic Approaches of Candida Infections

“…Regarding other plant-derived molecules, the Colombian essential oil Ruta graveolens showed high activity against clinically relevant Candida species; moreover, it demonstrated a remarkable synergizing effect in combination with traditional antifungal drugs [7]. In another study, the antifungal activity of the phenolic compounds ellagic acid and caffeic acid phenethyl ester was examined against C. auris isolates, where the caffeic acid phenethyl ester reduced the biomass and the metabolic activity of C. auris biofilm and decreased its adhesion to cultured human epithelial cells, indicating a potent antifungal and antivirulence effect [8]. It is noteworthy that one published paper focused on an animal-derived compound in terms of an antifungal effect.…”