Systematic Genetic Screen for Transcriptional Regulators of the Candida albicans White-Opaque Switch

Author:

Lohse Matthew B11,Ene Iuliana V2,Craik Veronica B1,Hernday Aaron D3,Mancera Eugenio1,Morschhäuser Joachim4,Bennett Richard J2,Johnson Alexander D15

Affiliation:

1. Department of Microbiology and Immunology, University of California, San Francisco, California 94158

2. Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912

3. Department of Molecular and Cell Biology, University of California, Merced, California 95343

4. Institut für Molekulare Infektionsbiologie, Universität Würzburg, D-97080, Germany

5. Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158

Abstract

Abstract 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.

Publisher

Oxford University Press (OUP)

Subject

Genetics

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