Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94102, USA.
Cell. 2012 Jan 20;148(1-2):126-38. doi: 10.1016/j.cell.2011.10.048.
A biofilm is an organized, resilient group of microbes in which individual cells acquire properties, such as drug resistance, that are distinct from those observed in suspension cultures. Here, we describe and analyze the transcriptional network controlling biofilm formation in the pathogenic yeast Candida albicans, whose biofilms are a major source of medical device-associated infections. We have combined genetic screens, genome-wide approaches, and two in vivo animal models to describe a master circuit controlling biofilm formation, composed of six transcription regulators that form a tightly woven network with ∼1,000 target genes. Evolutionary analysis indicates that the biofilm network has rapidly evolved: genes in the biofilm circuit are significantly weighted toward genes that arose relatively recently with ancient genes being underrepresented. This circuit provides a framework for understanding many aspects of biofilm formation by C. albicans in a mammalian host. It also provides insights into how complex cell behaviors can arise from the evolution of transcription circuits.
生物膜是由微生物组成的有组织的、有弹性的群体,其中单个细胞获得了一些特性,如抗药性,这些特性与悬浮培养中观察到的特性明显不同。在这里,我们描述和分析了控制致病性酵母白色念珠菌生物膜形成的转录网络,其生物膜是与医疗器械相关感染的主要来源。我们结合了遗传筛选、全基因组方法和两种体内动物模型,描述了一个控制生物膜形成的主控回路,该回路由六个转录调节剂组成,与约 1000 个靶基因形成了一个紧密编织的网络。进化分析表明,生物膜网络已经迅速进化:生物膜回路中的基因显著偏向于相对较新出现的基因,而古老的基因则相对较少。这个回路为理解白色念珠菌在哺乳动物宿主中形成生物膜的许多方面提供了一个框架。它还提供了关于复杂细胞行为如何从转录回路的进化中产生的见解。