The role of morphogenesis in the pathogenesis of systemic candidiasis

• Applicant: Professorin Dr. Ilse Denise Jacobsen
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2012 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 226040467

Candida albicans is an important human fungal pathogen which is increasingly identified as causative agent of sepsis in ICU patients. The ability of C. albicans to switch between yeast and hyphal growth forms is believed to be crucial for virulence during systemic infections and sepsis. In fact, mutants locked either in the yeast or hyphal phase are often strongly attenuated in virulence. Although it is clear that hyphal formation is essential for invasion into epithelial or endothelial cells in vitro, the role of filamentation in the pathogenesis of systemic candidiasis remains unknown. Our own data show that systemic infections of mice with the filamentationdeficient C. albicans mutant eed1can lead to mortality in the absence of hyphae. Other groups have identified additional filament-deficient mutants fully virulent or only moderately attenuated in the septic mouse model. These recent findings challenge the long-standing hypothesis that morphogenesis is essential for candidiasis. We aim to clarify the role of hyphal formation for pathogenesis of C. albicans sepsis by using defined molecular approaches including mutants in which morphogenesis is under the control of a regulatable promoter. The effect of morphology on virulence will be studied in different infection models, particularly with regard to the ability to induce tissue damage, interaction with immune cells and induction of sepsis.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Bernhard Hube