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TRR 124:  Pathogenic Fungi and their Human Host: Networks of Interaction - FungiNet

Subject Area Biology
Medicine
Term since 2013
Website Homepage
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 210879364
 
Invasive fungal infections (IFI) are a major threat worldwide. They are associated with unacceptably high mortality rates ranging from 30-90 % and have been estimated to kill about one and a half million people globally every year. Despite this, their diagnosis is often delayed or even overlooked. IFI are no longer limited to well-defined high-risk patient cohorts but also include patients with chronic obstructive lung disease as well as patients suffering from severe influenza infections, cytomegalovirus or COVID-19. Options for antifungal therapy are limited and mainly rely on only three classes of antifungals. In addition, we are faced with increasing antifungal drug resistance. In the CRC/TR FungiNet we aim to obtain a comprehensive insight into interaction networks of fungal pathogens with their human host, and identify potential new targets and tools for improved diagnostics and treatment. We focus on the polymorphic yeast Candida albicans and the filamentous fungus Aspergillus fumigatus because they are by far the most important causes of life-threatening invasive mycoses in Europe. As a model for emerging fungal pathogens from the Mucorales, we have included Lichtheimia corymbifera in our studies. These fungi have developed sophisticated, specific and unique pathogenicity mechanisms that enable them to colonize and infect the human body. For a comprehensive understanding of complex IFI, FungiNet considers three dimensions: (i) the biology of the pathogens, (ii) responses of the host’s immune system, and (iii) systems biology to uncover the dynamics of cause-effect relations of these pathogenic interactions. During the first two funding periods, we contributed to important discoveries towards understanding IFIs, e.g. by identifying the first peptide toxin in a human pathogenic fungus, determining fungal virulence factors and elucidating the cross talk between pathogens and immune cells. The third funding period will provide the unique opportunity to harvest the knowledge accumulated over the preceding years for translational projects to improve diagnostics and therapies. Importantly, the CRC/TR integrates university hospitals that treat the major groups of patients at high risk for fungal infections: Intensive care patients with increased susceptibility for Candida infections in Jena and hematology-oncology patients that are more susceptible to mould infections (A. fumigatus, L. corymbifera) in both Würzburg and Jena. Our link between basic research, clinics and bioinformatics expertise will allow the elucidation and development of diagnostic biomarkers to stratify the risk of patients for invasive mycoses, to further develop diagnostic approaches such as MALDI imaging of infected tissue and to establish novel therapeutic interventions. The latter will include the development of therapies based on immune cells and antifungal extracellular vesicles as well as the identification of novel targets for pharmacological antimycotic therapy.
DFG Programme CRC/Transregios

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Applicant Institution Friedrich-Schiller-Universität Jena
 
 

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