Uhl M Andrew, Biery Matt, Craig Nancy, Johnson Alexander D
Department of Microbiology and Immunology, University of California at San Francisco, 513 Parnassus Avenue, S-410, San Francisco, CA 94143-0414, USA.
EMBO J. 2003 Jun 2;22(11):2668-78. doi: 10.1093/emboj/cdg256.
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. Approximately 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.
白色念珠菌是最常见的人类真菌病原体。在此，我们利用单倍体不足和转座子诱变在该生物体中进行大规模功能丧失遗传筛选。我们鉴定出146个基因中的突变，这些突变影响其单细胞（酵母）形式和丝状生长形式之间的转换；这种转换似乎是白色念珠菌毒力的核心。所编码的蛋白质包括参与营养感知、信号转导、转录控制、细胞骨架组织和细胞壁构建的蛋白质。在筛选中鉴定出的基因中，约三分之一在酿酒酵母和其他模式生物中缺乏同源物，因此构成了候选抗真菌药物靶点。这些结果说明了在真正的病原体中进行正向遗传学研究的价值。
