Functional genomic analysis of genes important for Candida albicans fitness in diverse environmental conditions
Emily H. Xiong,
Xiang Zhang,
Huijuan Yan,
Henry N. Ward,
Zhen-Yuan Lin,
Cassandra J. Wong,
Ci Fu,
Anne-Claude Gingras,
Suzanne M. Noble,
Nicole Robbins,
Chad L. Myers,
Leah E. Cowen
Affiliations
Emily H. Xiong
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada
Xiang Zhang
Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA
Huijuan Yan
Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA
Henry N. Ward
Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA; Bioinformatics and Computational Biology Graduate Program, University of Minnesota, Minneapolis, MN 55455, USA
Zhen-Yuan Lin
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
Cassandra J. Wong
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
Ci Fu
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada
Anne-Claude Gingras
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
Suzanne M. Noble
Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA
Nicole Robbins
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada
Chad L. Myers
Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA; Bioinformatics and Computational Biology Graduate Program, University of Minnesota, Minneapolis, MN 55455, USA; Corresponding author
Leah E. Cowen
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Corresponding author
Summary: Fungal pathogens such as Candida albicans pose a significant threat to human health with limited treatment options available. One strategy to expand the therapeutic target space is to identify genes important for pathogen growth in host-relevant environments. Here, we leverage a pooled functional genomic screening strategy to identify genes important for fitness of C. albicans in diverse conditions. We identify an essential gene with no known Saccharomyces cerevisiae homolog, C1_09670C, and demonstrate that it encodes subunit 3 of replication factor A (Rfa3). Furthermore, we apply computational analyses to identify functionally coherent gene clusters and predict gene function. Through this approach, we predict the cell-cycle-associated function of C3_06880W, a previously uncharacterized gene required for fitness specifically at elevated temperatures, and follow-up assays confirm that C3_06880W encodes Iml3, a component of the C. albicans kinetochore with roles in virulence in vivo. Overall, this work reveals insights into the vulnerabilities of C. albicans.
