SPP 1160:  Colonisation and Infection by Human-pathogenic Fungi

• Subject Area: Medicine
• Term: from 2004 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5472023

In Europe, facultative pathogenic fungi are gaining importance as opportunistic infectious microorganisms of immunocompromised patients. These fungi either are ubiquitously distributed in the environment or colonise the mucosa of humans as saprophytic commensals.
The pathogenesis of fungal infections is determined by specific factors of the infecting fungus and defects of the innate immune system of the host. The relative contribution of these "factors" to a fungal infection is unclear. Therefore, the Priority Programme addresses the elucidation of infection mechanisms during disease caused by opportunistic fungal pathogens. Several aspects of fungal infection ranging from colonisation to infection will be investigated at the molecular level.
The genomes of important pathogenic fungal species were sequenced. This knowledge provides an excellent opportunity to analyse fungal infection mechanisms in a broad sense. The investigations within this Priority Programme will eventually lead to the identification of target molecules that will allow the development of improved diagnosis, therapy and prevention of human mycoses.
The Priority Programme is aimed at microbiologists, cell biologists and clinicians. Their experiences and methods will be used to solve the challenging questions.
The project proposals cover biological aspects of infections mainly of species of the fungal genera Candida, Aspergillus, Malassezia, Cryptococcus and Microsporidia important in Europe. The projects fall within one of the following three main research areas:
-- Metabolism and morphogenesis of human-pathogenic fungi
For the infectious process, important metabolic pathways, their regulation and important morphological changes have been investigated.
-- Characteristics relevant for fungal infection
Potential pathogenicity factors have been analysed at the gene and protein level including genomic approaches; their roles will be verified in infection models.
-- Interaction of human-pathogenic fungi with the immune system
Mechanisms of recognition of fungi by the innate immune system and subsequent immune reactions have been analysed in appropriate model systems.

• DFG Programme: Priority Programmes

Projects

• Analysis of the interaction between Aspergillus fumigatus and human dendritic cells and the induction of innate and adaptive immune responses to the pathogen (Applicant Einsele, Hermann )
• Analysis of the interaction between Aspergillus fumigatus and human immune effector cells and the induction of innate and adaptive immune responses to the pathogen (Applicant Einsele, Hermann )
• Carbon- and nitrogen utilisation of pathogenic Candida and Aspergillus species during pathogenesis (Applicant Brock, Matthias )
• Characterisation of the Cell Wall Proteome in Candida glabrata (Applicant Weig, Michael )
• Cross-Pathway Control, Nitrogen Metabolism and their Role in Pathogenicity of Aspergillus fumigatus (Applicant Krappmann, Sven )
• Holistic approach to genomics of human-pathogenic fungi: Data warehouse for integration of data on transcriptome, proteome and metabolome of Candida albicans and Aspergillus fumigatus (Applicants Brakhage, Axel ;  Hauser, Nicole )
• Identification and characterisation of virulence associated genes during oral infections with Candida albicans (Applicant Hube, Bernhard )
• Identification and characterization of virulence associated genes during vaginal infections with Candida albicans, focusing on the cell wall (Applicant Rupp, Steffen )
• Identification of TLR patterns and TLR-mediated epithelial protection mechanisms during localised candidosis (Applicant Schaller, Martin )
• Identification of virulence determinants of the human-pathogenic fungus Aspergillus fumigatus by proteome analysis (Applicant Brakhage, Axel )
• Immune evasion of the human pathogenic yeast Candida albicans (Applicant Zipfel, Peter F. )
• Intravital imaging of the interaction of the pathogenic fungus Aspergillus fumigatus with cells of the innate and adaptive immune system (Applicant Gunzer, Matthias )
• Koordination des Schwerpunktprogrammes "Kolonisation und Infektion durch humanpathogene Pilze" (Applicant Brakhage, Axel )
• Metabolism and morphogenesis of human pathogenic fungi (Applicant Brock, Matthias )
• Molecular analysis of the poly-telomeric CTA2 gene family of Candida albicans: Elucidation of genetic or epigenetic regulation of their differential expression, localisation and functional analyses in vitro and during the early phase of colonisation on porcine intestinal epithelium (Applicant Wendland, Jürgen )
• Pathogenicity factors of Malassezia furfur: genetic regulation of tryptophan-dependent secondary metabolites and their effect on immunocompetent and structural cells of human skin (Applicant Mayser, Peter )
• Pathogenicity factors of Malassezia furfur: genetic regulation of tryptophan-dependent secondary metabolites and their effect on immunocompetent and structural cells of human skin (Applicant Hube, Bernhard )
• Pmt proteins in host sensing of Candida albicans (Applicant Ernst, Joachim F. )
• Role of 3-hydroxyoxylipins, novel fungal metabolites of arachidonic acid, in Candida infection: potent effectors of fungal growth, virulence, and host cell survival (Applicant Nigam, Santosh )
• Role of Proinflammatory Fungal Lipoids in Fungal Inflammation (Applicant Schröder, Jens-Michael )
• Role of protein-mannosyl-transferases (PMTs) in virulence of Cryptococcus neoformans (Applicant Lengeler, Klaus Bruno )
• Structural and biochemical studies on the mechanism of CO2-sensing in the virulence of pathogenic fungi (Applicant Steegborn, Clemens )
• Studies on molecular mechanics of Candida albicans virulence gene regulation by the TEA transcription factor CaTec1p (Applicant Schröppel, Klaus )
• The parasitophorous vacuole of Encephalitozoon cuniculi: origin of the membrane and characterization of pore-forming proteins (Applicant Groß, Uwe )
• The role of ammonium permeases in control of dimorphism and in pathogenicity of Candida albicans (Applicant Morschhäuser, Joachim )

• Spokesperson: Professor Dr. Axel Brakhage