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.

Invasive fungal infections and the emergence of antifungal resistance pose significant challenges to public health. This study evaluates the antifungal activity of two 8-hydroxyquinoline derivatives, PH265 and PH276, against Cryptococcus spp., Candida auris, and Candida haemulonii. Using the EUCAST protocol, both compounds demonstrated broad-spectrum antifungal activity, with MICs ranging from 0.5 to 8 μg/mL. PH276 exhibited synergistic effects with fluconazole and caspofungin against C. haemulonii (FIC ≤ 0.5). The derivatives inhibited C. neoformans biofilm formation at higher concentrations and modulated polysaccharide capsule formation in Cryptococcus spp. In vivo toxicity assays in Tenebrio molitor, Galleria mellonella, and Caenorhabditis elegans revealed no significant adverse effects, with survival rates comparable to controls. These findings highlight PH265 and PH276 as promising antifungal agents with biofilm-disrupting properties, capsule-modulating effects, and low toxicity, supporting their potential for therapeutic development.