title: Antifungal Activity of Oleuropein against Candida albicans-The In Vitro Study.
abstract: In the present study we investigated activity of oleuropein, a complex phenol present in large quantities in olive tree products, against opportunistic fungal pathogenCandida albicans. Oleuropein was found to have in vitro antifungal activity with a minimal inhibitory concentration (MIC) value of 12.5 mg·mL-1. Morphological changes in the nuclei after staining with fluorescent DNA-binding dyes revealed that apoptosis was a primary mode of cell death in the analyzed samples treated with subinhibitory concentrations of oleuropein. Our results suggest that this antifungal agent targets virulence factors essential for establishment of the fungal infection. We noticed that oleuropein modulates morphogenetic conversion and inhibits filamentation ofC. albicans. The hydrophobicity assay showed that oleuropein in sub-MIC values has significantly decreased, in both aerobic and anaerobic conditions, the cellular surface hydrophobicity (CSH) ofC. albicans, a factor associated with adhesion to epithelial cells. It was also demonstrated that the tested compound inhibits the activity of SAPs, cellular enzymes secreted byC. albicans, which are reported to be related to the pathogenicity of the fungi. Additionally, we detected that oleuropein causes a reduction in total sterol content in the membrane ofC. albicanscells, which might be involved in the mechanism of its antifungal activity.
authors.affiliation: Agency for Medicinal Products and Medical Devices of Croatia (HALMED), Ksaverska cesta 4, HR-10000 Zagreb, Croatia. natasa.zoric@halmed.hr.
authors.forename: Nataša
authors.initials: N
authors.lastname: Zorić
authors.affiliation: Institute for Medical Research and Occupational Health, Ksaverska cesta 2, HR-10000 Zagreb, Croatia. nkopjar@imi.hr.
authors.forename: Nevenka
authors.initials: N
authors.lastname: Kopjar
authors.affiliation: Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Schrottova 39, HR-10000 Zagreb, Croatia. ivan.bobnjaric@gmail.com.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bobnjarić
authors.affiliation: Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Schrottova 39, HR-10000 Zagreb, Croatia. igor.horvat@gmail.com.
authors.forename: Igor
authors.initials: I
authors.lastname: Horvat
authors.affiliation: Agency for Medicinal Products and Medical Devices of Croatia (HALMED), Ksaverska cesta 4, HR-10000 Zagreb, Croatia. sinisa.tomic@halmed.hr.
authors.forename: Siniša
authors.initials: S
authors.lastname: Tomić
authors.affiliation: Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Schrottova 39, HR-10000 Zagreb, Croatia. ikosalec@pharma.hr.
authors.forename: Ivan
authors.initials: I
authors.lastname: Kosalec
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects* / Q000472:pathogenicity; D002448:Cell Adhesion / Q000187:drug effects*; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D057888:Iridoid Glucosides; D039823:Iridoids / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D031658:Olea / Q000737:chemistry; D028321:Plant Preparations / Q000494:pharmacology; D037521:Virulence Factors
chemical_list: D000935:Antifungal Agents; D057888:Iridoid Glucosides; D039823:Iridoids; D028321:Plant Preparations; D037521:Virulence Factors; C002769:oleuropein
keywords: Candida albicans; antifungal activity; oleuropein; virulence factors