Document Detail


Analysis of a fungus-specific transcription factor family, the Candida albicans zinc cluster proteins, by artificial activation.
MedLine Citation:
PMID:  23844834     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The zinc cluster proteins are a family of transcription factors that are unique to the fungal kingdom. In the pathogenic yeast Candida albicans, zinc cluster transcription factors control the expression of virulence-associated traits and play key roles in the development of antifungal drug resistance. Gain-of-function mutations in several zinc cluster transcription factors, which result in constitutive overexpression of their target genes, are a frequent cause of azole resistance in clinical C. albicans isolates. We found that zinc cluster proteins can also be artificially activated by C-terminal fusion with the heterologous Gal4 activation domain. We used this strategy to create a comprehensive library of C. albicans strains expressing all 82 zinc cluster transcription factors of this fungus in a potentially hyperactive form. Screening of this library identified regulators of invasive filamentous growth and other phenotypes that are important during an infection. In addition, the approach uncovered several novel mediators of fluconazole resistance, including the multidrug resistance regulator Mrr2, which controls the expression of the major C. albicans multidrug efflux pump CDR1. Artificial activation therefore is a highly useful method to study the role of zinc cluster transcription factors in C. albicans and other fungi of medical, agricultural and biotechnological importance.
Authors:
Rebecca Schillig; Joachim Morschhäuser
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-7-12
Journal Detail:
Title:  Molecular microbiology     Volume:  -     ISSN:  1365-2958     ISO Abbreviation:  Mol. Microbiol.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-7-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712028     Medline TA:  Mol Microbiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 John Wiley & Sons Ltd.
Affiliation:
Institut für Molekulare Infektionsbiologie, Universität Würzburg, Würzburg, Germany.
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