白念珠菌生物被膜形成的遗传调控机制

Genetic regulatory mechanisms of Candida albicans biofilm formation

摘要:

白念珠菌是人体重要的条件性致病真菌。形态的多样性和可塑性是白念珠菌典型的生物学特征，这与它的致病性、宿主适应能力以及有性生殖过程密切相关。白念珠菌生物被膜 (Biofilm) 是由不同形态细胞 (包括酵母型、菌丝和假菌丝) 以及胞外基质组成的致密结构，也是毒性和耐药性形成的重要因子。生物被膜对抗真菌药物、宿主免疫系统和环境胁迫因子等都表现出较强的抵抗力和耐受性，是临床上病原真菌感染防治的重大挑战。随着基因表达谱和遗传操作技术的发展，白念珠菌生物被膜的形成及其耐药性的获得所依赖的遗传调控通路和分子调控机制越来越清楚。主要包括MAPK和cAMP介导的信号途径以及Bcr1和Tec1等因子介导的转录调控。此外，白念珠菌生物被膜的形成与形态转换和有性生殖之间存在密切的联系。文中综述了白念珠菌生物被膜形成的遗传调控机制，重点介绍了细胞壁相关蛋白、转录因子和交配型对该过程的调控以及生物被膜的耐药机制。

Abstract:

Candida albicans is an important opportunistic fungal pathogen of humans. Phenotypic plasticity is a typical biological feature of C. albicans, which is associated with pathogenicity, host adaptation, and sexual reproduction. Biofilm of C. albicans is a complex community formed by different morphological types of cells (yeast, hyphae and pseudohyphae) and secreted extracellular matrix. C. albicans biofilms are intrinsically resistant to antifungal drugs, the host immune system, and environmental stresses. Biofilm is an important virulence factor and a major clinical challenge. With the development of new technologies in global gene expression profiles and genetic manipulation, the regulatory mechanisms that govern C. albicans biofilm development and drug resistance become more and more clear. Major regulatory mechanisms involve the MAPK and cAMP signaling pathways and transcriptional regulators such as Bcr1 and Tec1. In addition, morphological transitions and sexual reproduction are also involved in the regulation of biofilm development. In this review, we focus on the genetic regulatory mechanisms of biofilm including the roles of cell-wall related proteins, transcription factors, and the MTL locus. In the last section, we also summarize the mechanisms of drug resistance of biofilm in C. albicans.