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Haploinsufficiency‐based large‐scale forward genetic analysis of filamentous growth in the diploid human fungal pathogen C.albicans

M.Andrew Uhl, Matt Biery, Nancy Craig, Alexander D. Johnson

Author Affiliations

  1. M.Andrew Uhl1,
  2. Matt Biery2,
  3. Nancy Craig2 and
  4. Alexander D. Johnson*,1,3
  1. 1 Department of Microbiology and Immunology, University of California at San Francisco, 513 Parnassus Avenue, S‐410, San Francisco, CA, 94143‐0414, USA
  2. 2 Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
  3. 3 Department of Biochemistry and Biophysics, University of California at San Francisco, 513 Parnassus Avenue, S‐410, San Francisco, CA, 94143‐0414, USA
  1. *Corresponding author. E-mail: ajohnson{at}cgl.ucsf.edu
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Abstract

Candida albicans is the most prevalent human fungal pathogen. Here, we take advantage of haploinsufficiency and transposon mutagenesis to perform large‐scale loss‐of‐function genetic screen in this organism. We identified mutations in 146 genes that affect the switch between its single‐cell (yeast) form and filamentous forms of growth; this switch appears central to the virulence of C.albicans. The encoded proteins include those involved in nutrient sensing, signal transduction, transcriptional control, cytoskeletal organization and cell wall construction. Approxim ately one‐third of the genes identified in the screen lack homologs in Saccharomyces cerevisiae and other model organisms and thus constitute candidate antifungal drug targets. These results illustrate the value of performing forward genetic studies in bona fide pathogens.

  • Received October 24, 2002.
  • Revision received February 19, 2003.
  • Accepted March 28, 2003.
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