1. A Conserved C-Terminal Domain of the Aspergillus fumigatus Developmental Regulator MedA Is Required for Nuclear Localization, Adhesion and Virulence
- Author
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Donald C. Sheppard, Mark J. Lee, Fabrice N. Gravelat, Paolo Campoli, Qusai Al Abdallah, Se In Choe, and Stefanie D. Baptista
- Subjects
Spores ,Nuclear Localization Signals ,lcsh:Medicine ,Pathogenesis ,chemistry.chemical_compound ,Fungal Reproduction ,Gene Expression Regulation, Fungal ,Nuclear protein ,lcsh:Science ,0303 health sciences ,Fungal protein ,Multidisciplinary ,Virulence ,Microbial Growth and Development ,Fungal Diseases ,Fungal genetics ,Nuclear Proteins ,Spores, Fungal ,Cell biology ,Infectious Diseases ,Medical Microbiology ,Medicine ,Genome, Fungal ,Research Article ,Active Transport, Cell Nucleus ,Sequence alignment ,Mycology ,Biology ,Microbiology ,Fungal Proteins ,Molecular Genetics ,03 medical and health sciences ,Genetics ,Gene Regulation ,Amino Acid Sequence ,Transcription factor ,030304 developmental biology ,030306 microbiology ,Aspergillus fumigatus ,lcsh:R ,Fungi ,Protein Structure, Tertiary ,chemistry ,Biofilms ,lcsh:Q ,Gene Function ,Nuclear transport ,Nuclear localization sequence ,Transcription Factors ,MEDA - Abstract
MedA is a developmental regulator that is conserved in the genome of most filamentous fungi. In the pathogenic fungus Aspergillus fumigatus MedA regulates conidiogenesis, adherence to host cells, and pathogenicity. The mechanism by which MedA governs these phenotypes remains unknown. Although the nuclear import of MedA orthologues has been reported in other fungi, no nuclear localization signal, DNA-binding domain or other conserved motifs have been identified within MedA. In this work, we performed a deletion analysis of MedA and identified a novel domain within the C-terminal region of the protein, designated MedA(346-557), that is necessary and sufficient for nuclear localization of MedA. We further demonstrate that MedA nuclear localization is required for the function of MedA. Surprisingly, expression of the minimal nuclear localization fragment MedA(346-557) alone was sufficient to restore conidogenesis, biofilm formation and virulence to the medA mutant strain. Collectively these results suggest that MedA functions in the regulation of transcription, and that the MedA(346-557) domain is both necessary and sufficient to mediate MedA function.
- Published
- 2012
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