Systematic Genetic Screen for Transcriptional Regulators of the Candida albicans White-Opaque Switch.
The human fungal pathogen Candida albicans can reversibly switch between two cell types named "white" and "opaque," each of which is stable through many cell divisions. These two cell types differ in their ability to mate, their metabolic preferences and their interactions with the mammalian innate immune system. A highly interconnected network of eight transcriptional regulators has been shown to control switching between these two cell types. To identify additional regulators of the switch, we systematically and quantitatively measured white-opaque switching rates of 196 strains, each deleted for a specific transcriptional regulator. We identified 19 new regulators with at least a 10-fold effect on switching rates and an additional 14 new regulators with more subtle effects. To investigate how these regulators affect switching rates, we examined several criteria, including the binding of the eight known regulators of switching to the control region of each new regulatory gene, differential expression of the newly found genes between cell types, and the growth rate of each mutant strain. This study highlights the complexity of the transcriptional network that regulates the white-opaque switch and the extent to which switching is linked to a variety of metabolic processes, including respiration and carbon utilization. In addition to revealing specific insights, the information reported here provides a foundation to understand the highly complex coupling of white-opaque switching to cellular physiology.
Department of Microbiology and Immunology, University of California, San Francisco, California 94158.
Matthew B
MB
Lohse
Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912.
Iuliana V
IV
Ene
Department of Microbiology and Immunology, University of California, San Francisco, California 94158.
Veronica B
VB
Craik
Department of Molecular and Cell Biology, University of California, Merced, California 95343.
Aaron D
AD
Hernday
Department of Microbiology and Immunology, University of California, San Francisco, California 94158.
Eugenio
E
Mancera
Institut für Molekulare Infektionsbiologie, Universität Würzburg, D-97080, Germany.
Joachim
J
Morschhäuser
Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912.
Richard J
RJ
Bennett
Department of Microbiology and Immunology, University of California, San Francisco, California 94158 Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158 ajohnson@cgl.ucsf.edu.
Alexander D
AD
Johnson
D002176:Candida albicans / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D044127:Epigenesis, Genetic; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks / Q000235:genetics; D049770:Genes, Mating Type, Fungal / Q000235:genetics*; D005812:Genes, Switch; D006801:Humans; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
D014157:Transcription Factors
Candida albicans; transcription networks; transcriptional circuits; transcriptional regulation; white-opaque switching