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Transcription Factor SomA Is Required for Adhesion, Development and Virulence of the Human Pathogen Aspergillus
Chi-Jan Lin1, Christoph Sasse1, Jennifer Gerke1
1Department of Molecular Microbiology and Genetics, Institute of Microbiology & Genetics, Georg-August-University Göttingen, Göttingen, Germany.
Abstract:
The transcription factor Flo8/Som1 controls filamentous growth in Saccharomyces cerevisiae and virulence in the plant pathogen Magnaporthe oryzae. Flo8/Som1 includes a characteristic N-terminal LUG/LUH-Flo8-single-stranded DNA binding (LUFS) domain and is activated by the cAMP dependent protein kinase A signaling pathway. Heterologous SomA from Aspergillus fumigatus rescued in yeast flo8 mutant strains several phenotypes including adhesion or flocculation in haploids and pseudohyphal growth in diploids, respectively. A. fumigatus SomA acts similarly to yeast Flo8 on the promoter of FLO11 fused with reporter gene (LacZ) in S. cerevisiae. FLO11 expression in yeast requires an activator complex including Flo8 and Mfg1. Furthermore, SomA physically interacts with PtaB, which is related to yeast Mfg1. Loss of the somA gene in A. fumigatus resulted in a slow growth phenotype and a block in asexual development. Only aerial hyphae without further differentiation could be formed. The deletion phenotype was verified by a conditional expression of somA using the inducible Tet-on system. A adherence assay with the conditional somA expression strain indicated that SomA is required for biofilm formation. A ptaB deletion strain showed a similar phenotype supporting that the SomA/PtaB complex controls A. fumigatus biofilm formation. Transcriptional analysis showed that SomA regulates expression of genes for several transcription factors which control conidiation or adhesion of A. fumigatus. Infection assays with fertilized chicken eggs as well as with mice revealed that SomA is required for pathogenicity. These data corroborate a complex control function of SomA acting as a central factor of the transcriptional network, which connects adhesion, spore formation and virulence in the opportunistic human pathogen A. fumigatus.
Insights
The transcription factor SomA from Aspergillus fumigatus is essential for fungal growth, biofilm formation, and pathogenicity. It acts as a central regulator, connecting adhesion, spore development, and virulence in this opportunistic pathogen.
Area of Science:
- Mycology
- Molecular Biology
- Pathogenesis
Background:
- The transcription factor Flo8/Som1 regulates filamentous growth in yeast and virulence in fungi.
- Flo8/Som1 contains a conserved N-terminal LUFS domain and is activated by protein kinase A signaling.
- Heterologous expression of Aspergillus fumigatus SomA in yeast complements flo8 mutant phenotypes.
Purpose of the Study:
- To investigate the function of Aspergillus fumigatus SomA in fungal development, biofilm formation, and pathogenicity.
- To elucidate the role of the SomA/PtaB complex in Aspergillus fumigatus.
- To understand SomA's position within the transcriptional network controlling key fungal processes.
Main Methods:
- Functional complementation assays in Saccharomyces cerevisiae.
- Gene deletion and conditional expression studies in Aspergillus fumigatus.
- Biofilm formation and adherence assays.
- Transcriptional analysis using reporter gene fusions and gene expression studies.
- Infection assays in chicken eggs and mice.
Main Results:
- Aspergillus fumigatus SomA complements yeast flo8 mutant phenotypes, including adhesion and pseudohyphal growth.
- Loss of somA in A. fumigatus leads to impaired growth, blocked asexual development, and defects in biofilm formation.
- SomA physically interacts with PtaB, and the SomA/PtaB complex is crucial for biofilm formation.
- SomA regulates transcription factors involved in conidiation and adhesion.
- SomA is essential for pathogenicity in both chicken egg and mouse infection models.
Conclusions:
- SomA is a critical regulator in Aspergillus fumigatus, controlling a network of genes involved in adhesion, spore formation, and virulence.
- The SomA/PtaB complex plays a key role in biofilm development.
- SomA is a central factor connecting multiple essential processes for the survival and pathogenicity of this opportunistic human pathogen.
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