A Conserved C-Terminal Domain of the Aspergillus fumigatus Developmental Regulator MedA Is Required for Nuclear Localization, Adhesion and Virulence

Qusai Al Abdallah, Se In Choe, Paolo Campoli, Stefanie Baptista, Fabrice N. Gravelat, Mark J. Lee, Donald C. Sheppard

Research output: Contribution to journalArticle

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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 MedA346-557, 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 MedA346-557 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 MedA346-557 domain is both necessary and sufficient to mediate MedA function.

Original languageEnglish (US)
Article numbere49959
JournalPloS one
Volume7
Issue number11
DOIs
StatePublished - Nov 21 2012

Fingerprint

Aspergillus fumigatus
Aspergillus
Fungi
Virulence
adhesion
virulence
Adhesion
Nuclear Localization Signals
Cell Nucleus Active Transport
Biofilms
Transcription
Genes
Genome
Phenotype
DNA
fungi
Meda
Proteins
nuclear localization signals
DNA-binding domains

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

A Conserved C-Terminal Domain of the Aspergillus fumigatus Developmental Regulator MedA Is Required for Nuclear Localization, Adhesion and Virulence. / Al Abdallah, Qusai; Choe, Se In; Campoli, Paolo; Baptista, Stefanie; Gravelat, Fabrice N.; Lee, Mark J.; Sheppard, Donald C.

In: PloS one, Vol. 7, No. 11, e49959, 21.11.2012.

Research output: Contribution to journalArticle

Al Abdallah, Qusai ; Choe, Se In ; Campoli, Paolo ; Baptista, Stefanie ; Gravelat, Fabrice N. ; Lee, Mark J. ; Sheppard, Donald C. / A Conserved C-Terminal Domain of the Aspergillus fumigatus Developmental Regulator MedA Is Required for Nuclear Localization, Adhesion and Virulence. In: PloS one. 2012 ; Vol. 7, No. 11.
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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 MedA346-557, 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 MedA346-557 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 MedA346-557 domain is both necessary and sufficient to mediate MedA function.",
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AU - Choe, Se In

AU - Campoli, Paolo

AU - Baptista, Stefanie

AU - Gravelat, Fabrice N.

AU - Lee, Mark J.

AU - Sheppard, Donald C.

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