Identification of Candida albicans genes that induce Saccharomyces cerevisiae cell adhesion and morphogenesis
Identification of Candida albicans genes that induce Saccharomyces cerevisiae cell adhesion and morphogenesis
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DOI：
10.1021/bp050236c
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发表时间：
2005-11-01
影响因子：
2.9
通讯作者：
Palecek, SP
中科院分区：
文献类型：
--
作者：
Li, F;Palecek, SP
形态发生和对宿主组织和医疗器械的黏附导致了白色念珠菌的毒力，这是从人类分离出的最常见的真菌病原体。然而，由于缺乏有效的分子和遗传工具，白念珠菌黏附和形态发生的分子机制的鉴定一直受到影响。酿酒酵母具有良好的遗传学和基因表达系统，为研究白色念珠菌的黏附和形态发生提供了一个很有吸引力的模型系统。为了深入了解白念珠菌黏附和形态发生的遗传机制，我们使用平行平板流动室筛选并定量表征了表达白念珠菌基因组文库的黏附缺陷非丝状Flo8 Delta S.cerevisiae菌株对聚苯乙烯的黏附。我们在酿酒酵母中鉴定了六个能够促进细胞黏附和假菌丝发育的白色念珠菌基因。我们还分析了这些黏附促进基因调控FLO11表达的能力，FLO11编码一种内源的酿酒酵母黏附素。一个白色念珠菌基因EAP1似乎直接介导黏附和形态发生，而其余五个基因(EAP2、SWI1、MSB1、AAF1和TEC1)上调内源酿酒酵母粘附素的表达。这些结果表明，酿酒酵母是一个有用的系统，可用于调控白色念珠菌黏附和形态发生的因素的分子表征，基于平行平板流动小室的黏附分析可以与遗传筛选结合使用，以确定调控真菌细胞黏附的分子机制。
Morphogenesis and adhesion to host tissues and medical devices contribute to the virulence of Candida albicans, the most common fungal pathogen isolated from humans. However, identification of molecular mechanisms of C. albicans adhesion and morphogenesis has been impaired by the lack of effective molecular and genetic tools available for this organism. Saccharomyces cerevisiae provides an attractive model system for studying C. albicans adhesion and morphogenesis because of its well-characterized genetics and gene expression systems. To gain insight into the genetic mechanisms of C. albicans adhesion and morphogenesis, we used a parallel plate flow chamber to screen and quantitatively characterize attachment to polystyrene of an adhesion-deficient nonfilamentous flo8 Delta S. cerevisiae strain expressing a C. albicans genomic library. We identified six C. albicans genes that are capable of promoting cell adhesion and pseudohyphal development in S. cerevisiae. We also analyzed the ability of these adhesion-promoting genes to regulate the expression of FLO11, which encodes an endogenous S. cerevisiae adhesin. One C. albicans gene, EAP1, appears to directly mediate adhesion and morphogenesis while the remaining five (EAP2, SWI1, MSB1, AAF1, and TEC1) upregulate expression of endogenous S. cerevisiae adhesins. These results suggest that S. cerevisiae is a useful system for molecular characterization of factors that regulate C. albicans adhesion and morphogenesis and that parallel plate flow chamber-based adhesion assays can be used in conjunction with genetic screens to identify molecular mechanisms regulating fungal cell adhesion.