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.
Highlights
We initially evaluated the antifungal activity of seven polyphenols against a Candida spp. panel, including a number of C. auris isolates, which exhibited high-level resistance to fluconazole (Supplementary Table S2)
The results demonstrated that polyphenol ellagic acid and caffeic acid phenethyl ester are more effective and present antifungal against C. auris and C. albicans
The in vivo analysis revealed the anti-infective potential of ellagic acid (EA) and caffeic acid phenethyl ester (CAPE) by protecting G. mellonella from the pathogenicity of C. auris and C. albicans
Summary
Introduction published maps and institutional affilFungal infections are responsible for high mortality and morbidity, especially among immunocompromised patients, and their incidence has risen in the last few decades [1,2,3].Candida spp. remain the most common cause of invasive fungal infections, and candidiasis is ranked as the fourth leading cause of bloodstream infections in the United States [2,4,5,6].Among Candida spp., Candida auris has emerged as a highly drug-resistant pathogen in recent years, while Candida albicans is associated with more than 50% of human candidiasis [2,7]. Fungal infections are responsible for high mortality and morbidity, especially among immunocompromised patients, and their incidence has risen in the last few decades [1,2,3]. Candida spp. remain the most common cause of invasive fungal infections, and candidiasis is ranked as the fourth leading cause of bloodstream infections in the United States [2,4,5,6]. Among Candida spp., Candida auris has emerged as a highly drug-resistant pathogen in recent years, while Candida albicans is associated with more than 50% of human candidiasis [2,7]. C. auris was first described in 2009 as an isolate from the ear canal of a patient in. Invasive infections have increased, even outcompeting the most common fungal pathogen
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