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

Abstract

<i>Candida auris</i> 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 <i>Candida auris</i>. We also tested against <i>C. albicans</i>. 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 <i>C. auris</i> strains. Killing kinetics determined that after 4 h treatment with CAPE, there was a complete reduction of viable <i>C. auris</i> cells compared to fluconazole. Both compounds might act by modifying the fungal cell wall. CAPE significantly reduced the biomass and the metabolic activity of <i>C. auris</i> biofilm and impaired <i>C. auris</i> adhesion to cultured human epithelial cells. Furthermore, both compounds prolonged the survival rate of <i>Galleria mellonella</i> infected by <i>C. auris</i> (<i>p</i> = 0.0088 for EA at 32 mg/kg and <i>p</i> = 0.0028 for CAPE at 4 mg/kg). In addition, EA at 4 μg/mL prolonged the survival of <i>C. albicans</i>-infected <i>Caenorhabditis elegans</i> (<i>p</i> < 0.0001). CAPE was not able to prolong the survival of <i>C. albicans</i>-infected <i>C. elegans.</i> These findings highlight the antifungal and antivirulence effects of EA and CAPE against <i>C. auris</i>, and warrant further investigation as novel antifungal agents against drug-resistant infections.