טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentAvitan Daniel
SubjectA Novel Inducer of Hyphal Morphogenesis in Candida
Albicans
DepartmentDepartment of Medicine
Supervisor Dr. Daniel Kornitzer
Full Thesis textFull thesis text - English Version


Abstract

Candida albicans is a pathogenic fungus that can switch between yeast (oval-shaped cells) and hyphae (elongated, filamentous cells) in response to a variety of external stimuli. This ability has been long associated with virulence and pathogenesis of Candida albicans. Well-characterized stimuli include elevated temperature (37°C), exposure to serum, N-acetylglucosamine, alkaline pH, CO2, and growth in low nitrogen media. Like all organisms, C. albicans requires several metals as essential cofactors for cellular enzymes activity, chief among them iron. The metal requirements are typically investigated using chelators such as EDTA (chelator for Mg2 and Zn2), EGTA (Ca2), BCS (Cu2), ferrozine, and BPS (Fe2). The use of the latter two chelators revealed the ability of C. albicans to utilize hemoglobin as an alternative iron source. Here we identify the iron chelator BPS as a novel inducer of hyphae. Although hemoglobin is added to the media with BPS to allow growth, we eliminated the possibility that hemoglobin is responsible for this morphological change. Rather, it is the addition of BPS that induces hyphae. Our results also reduced the likelihood that the induction of hyphal morphogenesis is due to the chelation of any of the metals BPS chelates outside of the cell. We also addressed the mechanisms by which BPS induces hyphal morphogenesis by identifying genes involves in this new pathway. Through an unbiased genetic screen for mutants defective in BPS-induced filamentation, we identified two genes, YAK1 and orf19.384. Both proteins' homologs in other organisms such as Saccharomyces cerevisiae, Drosophila melanogaster, and Homo sapiens were shown to interact with each other, suggesting that this is also the case in C. albicans. The observation that they are both involved in the same filamentation pathway supports this possibility.