Plant Fungi Interactions (prof. Bruno Cammue)
Research at PFI was initiated in the early 1990s with an extensive screening for novel antimicrobial plant peptides, and resulted in the discovery of several types of novel antifungal proteins. On one of them, named the plant defensins (PDFs), pioneering research was continued. PDFs are small, basic, cysteine-rich antifungal peptides that are structurally related to insect and mammalian defensins. They are active against a broad range of phytopathogenic fungi (e.g. Botrytis cinerea, Fusarium spp., Alternaria spp.) and even human pathogens (e.g. Candida albicans and Aspergillus flavus), whereas they are nontoxic to plant and mammalian cells. Primarily based on PDFs studies, research at PFI was further developed in the late 1990s in two distinct research units, focussed on either side of the plant-fungus interaction.
PFI-Plant research unit
The discovery of different types of PDFs in Arabidopsis thaliana significantly stimulated our research on their expression and function. For example, the discovery of the plant defensin At PDF1.2a and the corresponding signaling pathways involved in its induction broadened the general insight in induced defense mechanisms in plants. The corresponding gene is now world-wide used as a marker for ethylene/jasmonate controled responses in plants. To support this research also different molecular tools and approaches were developed optimizing plant transformation and molecular breeding.
Current research is still focussing on (> 320) PDF-like peptides in Arabidopsis using up-to-date approaches including genomics, transcriptomics, interactomics, genome editing (e.g. via CRISPR-Cas), plant phenotyping, etc..., primarily aiming at discovering their in planta role. This research is recently broadened to other types of stress-induced peptides (SIPs, LSUs, ...). Our expertise on resistance mechanisms, mainly in A. thaliana and focusing on resistance to necroptrophic fungi, allowed us to successfully use this model plant for agronomically important crops/diseases (e.g. Fusarium oxysporum in banana, Cercospora beticola in sugarbeet, Cochliobolus heterostrophus in corn). Based on the same expertise some years ago we also initiated research on defense mechanisms induced by biocontrol organisms, the so-called induced systemic response (ISR). This research is based on comparative transcriptome studies both in the model plant A. thaliana and in crops (e.g. tomato, lettuce), involves both biotic and abiotic biocontrol agents and is mainly directed to different necroptrophic pathogens. This resulted in a high-throughput ISR screening platform which allows identification of novel biocontrol agents and the unraveling of their underlying mechanisms. Currently the potential of these biocontrol agents is evaluated in different crop-pathosystems (e.g. tomato - Botrytis cinerea, corn - Cochliobolus heterostrophus, soybean - Sclerotinia sclerotiorum, ...).
Since January 1, 2014 the PFI Plant research unit is affiliated with the VIB center of “Plant Systems Biology” (headed by prof. Dirk Inzé; http://www.psb.ugent.be)
PFI-Fungus/yeast unit (co-coordinated by dr. Karin Thevissen)
Using genetic screens and specific biochemical assays, mainly on the model yeast Saccharomyces cerevisiae, we were able to unravel the mode of antifungal activity (MOA) of some PDFs, including the discovery of specific sphingolipids as primary binding sites in the fungal membrane, the induction of reactive oxigen species and subsequent apoptosis, and membrane permeabilization. Currently we are still refining this MOA for specific PDFs and extrapolate them to both important plant pathogens (e.g. Fusarium oxysporum) and human pathogens (e.g. Candida albicans). The latter findings allowed us to extend this research for other plant peptides (such the above mentioned SIPs) and for synthetic antimycotic compounds, and on different tolerance/resistance mechanisms occurring in both fungal planktonic cells and biofilms. Based on accumulated expertise, we are aiming at the development of drugs including antimycotics, anti-biofilm compounds, anti-apoptotic drugs, etc... as well as of potentiators of such drugs. We therefore apply large-scale screening of selected compound libraries, structure-activity relationship analyses, mode of action studies, development of humanized yeast models and general drugability tests. Accumulated knowledge on the MOA of antimycotics and antibiofilm compounds is currently valorized in the development of specific sensors for nano-diagnosis of human fungal infections, and of next generation implants (based on either coating or controlled release of bioactive compounds), respectively. Moreover, fundamental insights in either their anti- and pro-apoptotic characteristics allowed us to set up yeast model systems relevant for e.g. human diseases, and as such to identify novel compounds to treat them.