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白色念珠菌转录因子Bcr1p对细胞表面基因和生物膜形成的调控

Regulation of cell-surface genes and biofilm formation by the C. albicans transcription factor Bcr1p.

作者信息

Nobile Clarissa J, Mitchell Aaron P

机构信息

Department of Microbiology, Columbia University, New York, NY 10032, USA.

出版信息

Curr Biol. 2005 Jun 21;15(12):1150-5. doi: 10.1016/j.cub.2005.05.047.

Abstract

The impact of many microorganisms on their environment depends upon their ability to form surface bound communities called biofilms [1]. Biofilm formation on implanted medical devices has severe consequences for human health by providing both a portal of entry and a sanctuary for invasive bacterial and fungal pathogens [1 and 2]. Biofilm regulators and adherence molecules are extensively defined for many bacterial pathogens [3, 4, and 5], but not for fungal pathogens such as Candida albicans. Elongated filaments called hyphae are a prominent feature of C. albicans biofilms, and known genes that promote biofilm formation are required for hyphal development [2, 6, 7 and 8]. From a new library of transcription-factor mutants, we identify Bcr1p, a zinc finger protein required for formation of biofilms but not hyphae. Expression analysis shows that Bcr1p activates cell-surface protein and adhesin genes, including several induced during hyphal development. BCR1 expression depends upon the hyphal regulator Tec1p. Thus, BCR1 is a downstream component of the hyphal regulatory network that couples expression of cell-surface genes to hyphal differentiation. Our results indicate that hyphal cells are specialized to present adherence molecules that support biofilm integrity.

摘要

许多微生物对其生存环境的影响取决于它们形成被称为生物膜的表面附着群落的能力[1]。植入式医疗设备上生物膜的形成对人类健康具有严重影响,因为它为侵入性细菌和真菌病原体提供了一个进入途径和庇护所[1和2]。生物膜调节因子和黏附分子在许多细菌病原体中已有广泛定义[3、4和5],但在白色念珠菌等真菌病原体中却并非如此。被称为菌丝的细长丝状物是白色念珠菌生物膜的一个显著特征,促进生物膜形成的已知基因是菌丝发育所必需的[2、6、7和8]。通过一个新的转录因子突变体文库,我们鉴定出Bcr1p,一种形成生物膜而非菌丝所必需的锌指蛋白。表达分析表明,Bcr1p激活细胞表面蛋白和黏附素基因,包括在菌丝发育过程中诱导表达的几个基因。BCR1的表达依赖于菌丝调节因子Tec1p。因此,BCR1是菌丝调节网络的一个下游组分,它将细胞表面基因的表达与菌丝分化联系起来。我们的结果表明,菌丝细胞专门用于呈现支持生物膜完整性的黏附分子。

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