Metergoline-induced cell death in Candida krusei

Abstract

Metergoline possesses potent antifungal activity against Candida krusei, a notorious yeast species that is inherently resistant to the common antifungal agents. In an attempt to elucidate the action mechanisms of metergoline, the present study was designed to investigate its effects on a number of classical markers of apoptosis in C. krusei. The results showed that transient exposure (2h) to metergoline led to a massive intracellular accumulation of reactive oxygen species (ROS) and depolarization of mitochondrial membrane potential in a concentration-dependent fashion. Analyses of the treated fungal cells after prolonged incubation (12h) with metergoline by flow cytometry and fluorescence microscopy clearly demonstrated phosphatidylserine externalization, the presence of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling-positive cells and fungal cells undergoing necrosis. Taken together, our data provide evidence that metergoline elicited cell death process in C. krusei through elevation of the intracellular ROS level and perturbation of mitochondrial homeostasis, followed by damage of nucleus and eventual cell demise.