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Project

THE ELUCIDATION OF SUBCELLULAR IRON HOMEOSTASIS IN CANDIDA ALBICANS IN THE PRESENCE AND ABSENCE OF THE ANTIFUNGAL DRUG FLUCONAZOLE

C. albicans forms a part of the natural human microbiome and is predominantly found in the gastrointestinal tract, on the skin and on mucosal surfaces. However, in some circumstances, C. albicans is able to switch to a pathogenic lifestyle resulting in candidiasis. Especially immunocompromised patients as well as patients undergoing transplant surgery are the main risk groups for a Candida infection. A problem currently observed in hospitals is the increase in azole drug resistance. An important reason for the rapid appearance of fluconazole resistance is the fact that fluconazole is a fungistatic drug against C. albicans. Actually a subpopulation of cells even grows slowly in the presence of high fluconazole concentrations. In work performed in the host laboratory it was found that the level of iron is important for this tolerance mechanisms as removal of iron from the cell (e.g. by adding doxycycline or other iron chelators) converts the fungistatic character of fluconazole into a fungicidal drug (Fiori et al. AAC 2012). A screening in the model yeast Saccharomyces cerevisiae showed that mitochondria play an important role in this iron mediated tolerance, which was then also confirmed for C. albicans. How iron is mediating this process is unknown. Is iron influx into mitochrondria important? How is this regulated? Is iron homeostasis in the cell and between organelles important? What mechanism is linking fluconazole with the iron regulon and how does this affect tolerance?

Date:9 Mar 2021 →  30 Jan 2023
Keywords:subcellular iron homeostasis, candida albicans, fluconazole
Disciplines:Mycology
Project type:PhD project