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AfuSomA transcriptional network in human pathogen Aspergillus fumigatus

Control of asexual development, adhesion and virulence

dc.contributor.advisorBraus, Gerhard Prof. Dr.
dc.contributor.authorLin, Chi-Jan
dc.titleAfuSomA transcriptional network in human pathogen Aspergillus fumigatusde
dc.title.alternativeControl of asexual development, adhesion and virulencede
dc.contributor.refereePöggeler, Stefanie Prof. Dr.
dc.description.abstractengFungal development is regulated by environmental stimuli via various signaling pathways. For instance, the cyclic AMP dependent protein kinase A (PKA) cascade is controlling development or pathogenesis in fungi as filamentous growth in backer yeast Saccharomyces cerevisiae or pathogenesis in plant pathogenic fungus Magnaporthe oryzae. The cAMP/PKA downstream target Flo8/Som1 containing a conserved LUG/LUH-Flo8-single-stranded DNA binding (LUFS) domain is required for morphological development and virulence. In this study the FLO8 homolog, AfusomA of the human opportunistic pathogenic fungus Aspergillus fumigatus was investigated. Heterologous expression of the AfuSomA encoding gene complemented invasive growth (cell-surface adhesion) or flocculation (cell-cell adhesion) in haploid or pseudohyphal growth in diploid Δflo8 S. cerevisiae yeast strains. AfuSomA and ScFlo8 regulate the expression of the ScFLO11 gene encoding flocculin as major component for adhesion by binding to similar regions on its promoter. These results indicate that AfuSomA and ScFlo8 share a similar function in yeast. Loss of the encoding AfuSomA resulted in a slow growth phenotype and a block in asexual development in A. fumigatus. Only aerial hyphae without further differentiation could be formed in AfusomA null mutant. An abolishment of conidiation was verified by a conditional expression of AfusomA using the inducible Tet-on system. Adherence to the host is an important step for pathogenesis. Adhesion assay with conditional expression strain indicated that AfuSomA is required for adherence to plastic surfaces. Infection of fertilized chicken eggs revealed that AfuSomA is required for pathogenicity. Transcription analysis showed that AfuSomA regulates expression of several transcription factors which have been shown to regulate conidiation and adhesion in A. fumigatus. GFP-Trap with AfuSomA leads to the identification of nucleolar proteins and PtaB (ScMfg1) which the yeast homolog forms complex with ScFlo8. Expression of putative adhesins was down regulated in AfusomA null strain. Single or multiple deletions of putative adhesins showed normal conidiation and
dc.contributor.coRefereeGroß, Uwe Prof. Dr.
dc.subject.engAspergillus fumigatusde
dc.affiliation.instituteGöttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB)de
dc.subject.gokfullBiologie (PPN619462639)de

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