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

**Ibrahim Alfarrayeh 1,2,\* , Edit Pollák 3 , Árpád Czéh 4 , András Vida <sup>4</sup> , Sourav Das <sup>5</sup> and Gábor Papp <sup>1</sup>**


**Abstract:** This study investigated the effect of CAPE on planktonic growth, biofilm-forming abilities, mature biofilms, and cell death of *C. albicans*, *C. tropicalis*, *C. glabrata*, and *C. parapsilosis* strains. Our results showed a strain- and dose-dependent effect of CAPE on *Candida*, and the MIC values were between 12.5 and 100 µg/mL. Similarly, the MBIC values of CAPE ranging between 50 and 100 µg/mL highlighted the inhibition of the biofilm-forming abilities in a dose-dependent manner, as well. However, CAPE showed a weak to moderate biofilm eradication ability (19-49%) on different *Candida* strains mature biofilms. Both caspase-dependent and caspase-independent apoptosis after CAPE treatment were observed in certain tested *Candida* strains. Our study has displayed typical apoptotic hallmarks of CAPE-induced chromatin margination, nuclear blebs, nuclear condensation, plasma membrane detachment, enlarged lysosomes, cytoplasm fragmentation, cell wall distortion, whole-cell shrinkage, and necrosis. In conclusion, CAPE has a concentration and strain-dependent inhibitory activity on viability, biofilm formation ability, and cell death response in the different *Candida* species.

**Keywords:** CAPE; *Candida*; antifungal; biofilm; apoptosis
