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

被引:145
作者
Uhl, MA
Biery, M
Craig, N
Johnson, AD
机构
[1] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA
[3] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Howard Hughes Med Inst, Baltimore, MD 21205 USA
关键词
Candida albicans; filamentous growth; haploinsufficiency;
D O I
10.1093/emboj/cdg256
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2668 / 2678
页数:11
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