Poster Presenter

Mechanistic Studies on the Metergoline-Induced Death on Candida Krusei
Kai KANG, Wing-Ping FONG,Paul Wai-Kei TSANG
Hong Kong

Candida krusei is inherently resistant to fluconazole. Although it accounts for only 2% infection in all candidemia, candidal infections associated with C. krusei have the highest mortality rate (30-60%) because of the decreased susceptibility to amphotericin B and caspofungin. In an attempt to search for novel antifungal agents, we have previously found that metergoline, a serotonin receptor antagonist, was effective in inhibiting the growth of C. krusei. The action mechanism was explored in the present study. After treatment with metergoline for 3 hours, the level of intracellular reactive oxygen species (ROS) increased by 2-fold. Such an increase could be prevented by the presence of ascorbic acid and mannitol. These antioxidants protected C.krusei against metergoline, as shown by a 4-fold increase in the minimum inhibitory concentration (MIC) value. Depolarization of mitochondrial membrane potential, was observed by flow cytometric analysis in the metergoline-treated C. krusei. Positive result was also obtained on the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. These two pieces of evidence suggest that metergoline may promote an apoptosis-like cell death mechanism in C. krusei.