Funding tool: Basic research projects
Project-ID: LS13-026
Project start: 01. Dezember 2014
Project end: will follow
Runtime: 36 months / finished
Funding amount: € 208.000,00

Brief summary:

Novel antifungal agents focussing on Candida spp.
Acronym: Cantifun Candida antifungals
Background: Candida spp including C. glabrata are widespread human fungal pathogens. Candidiasis affects mostly elderly and immune compromised patients. Especially C. glabrata has a high intrinsic stress resistance and is highly adapted to the human host. Common antifungal therapies are only party effective and next generation compounds are required.
Specific Aims: Characterization of human fungal pathogens in Vienna/Lower Austria region. As a ressource, we have access to the clinical Candida collection of the Vienna General Hospital. In this approach we will characterize the clinically isolated strains and determine their response patterns to environmental cues. It is important for microorganisms to cope with adverse conditions like drought, heat, acid, and oxidative stress. We have analysed stress resistance mechanisms of C. glabrata and have recently defined the hyperosmolarity responsive Hog pathway as a central resistance mechanism ex vivo and in an in vivo infection model. Consequently we will further analyze the role of this pathway for virulence and successful persistence on surfaces.
In addition, to break new ground for development of specific antifungals we will aim at the identification of compounds affecting the survival of C. glabrata and related fungi. To this end we propose to establish a screen for antifungal peptides generated by genetic means using yeast as a synthesis and test system. Using yeast the mode of action of the growth inhibiting or lethal peptides will be determined by systematic genetic analysis. Peptides targeting fungal specific processes will be developed further and their function will be addressed by expressing these peptides in C. glabrata and possibly other genetically accessible fungi like A. gossypii and A. nidulans.
Outcome: Our research will assess for the first time the local strains in Lower Austria and Vienna providing a basis of future development of specific Candida antifungals. Furthermore, we will establish a method for development of antifungal strategies and possibly identify antifungal peptides effective against human pathogen fungi and other ascomycete pathogen species.

Keywords:
1) Inhibitors, biologically active substances, drugs 2) Saccharomyces cerevisiae, Aspergillus nidulans, fungi, 3) Combinatorial synthesis, high throughput screening, systematic genetics