Antifungal activity of Eugenia dysenterica (Mart.) DC. (Myrtaceae) alone or in combination with antifungal agents against Candida (Candidozyma) auris.

Candida (Candidozyma) auris is a multidrug-resistant fungal pathogen associated with high mortality and limited treatment options. Eugenia dysenterica, a medicinal plant from the Brazilian Cerrado traditionally used for gastrointestinal ailments, is rich in bioactive phenolics with potential therapeutic applications. To evaluate the chemical composition, antifungal activity, mechanisms of action, and in vivo effects of ethanolic leaf extract of E. dysenterica (Ed-EE) against C. auris. Ed-EE was analyzed for phenolic and flavonoid content. Its antifungal activity and interactions with amphotericin B (AmB) and fluconazole (FLC) were tested using microdilution and checkerboard assays. Mechanisms of action were explored through membrane integrity and efflux pump inhibition assays. Hemolysis assay was performed to assess hemocompatibility. In vivo toxicity and efficacy were evaluated using Tenebrio molitor larvae. Ed-EE exhibited fungistatic activity against C. auris, with a MIC of 32 μg/mL. When combined with AmB, a synergistic effect was observed (FICI = 0.5), reducing the MICs to 8 μg/mL for Ed-EE and 0.5 μg/mL for AmB. Mechanistic assays indicated moderate membrane disruption and efflux pump inhibition. Hemolysis and in vivo assays using T. molitor larvae showed survival rates above 80 %, confirming low toxicity. However, Ed-EE did not significantly inhibit biofilm formation at tested concentrations. Ed-EE exhibits promising antifungal activity against C. auris, particularly in synergy with AmB, and demonstrates a favorable safety profile as potential adjuvant therapy for resistant fungal infections.