Genetic control of conventional and pheromone-stimulated biofilm formation in Candida albicans.
Genetic control of conventional and pheromone-stimulated biofilm formation in Candida albicans.
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DOI：
10.1371/journal.ppat.1003305
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发表时间：
2013
期刊：
影响因子：
6.7
通讯作者：
Bennett RJ
中科院分区：
文献类型：
--
作者：
Lin CH;Kabrawala S;Fox EP;Nobile CJ;Johnson AD;Bennett RJ
白色念珠菌可以随机在白色和不透明两种表型之间切换。不透明细胞是白色念珠菌性功能的形式，因此在信息素存在的情况下进行有效的极化生长和交配。相比之下，白细胞不能交配，但在一组特殊的条件下，会被诱导形成生物膜，以响应信息素。在这项工作中，我们比较了这种“信息素刺激”生物膜和“传统”白色念珠菌生物膜的遗传调节。特别是，我们研究了六个转录调控因子(Bcr1、BRG1、Efg1、Tec1、Ndt80和Rob1)组成的网络，它们在信息素刺激的生物膜形成中发挥了潜在的作用。我们发现六个转录因子中的四个(Bcr1，BRG1，Rob1和Tec1)促进常规和信息素刺激的生物膜的形成，表明它们在细胞凝聚力和生物膜发育中发挥普遍作用。此外，我们还鉴定了信息素刺激生物膜的主要转录调控因子为白色念珠菌Cph1，酿酒酵母STE12的同源基因。Cph1调节白色念珠菌不透明细胞中的交配，在这里我们表明Cph1对于信息素刺激的白细胞生物膜的形成也是必不可少的。相比之下，Cph1对于传统生物膜的形成是必不可少的。通过转录图谱和遗传分析进一步研究了信息素刺激的生物膜形成的调控。这些研究确定了196个基因，它们是在生物膜形成过程中由信息素信号诱导的。这些基因之一，HGC1，被证明是形成常规生物膜和信息素刺激的生物膜所必需的。综上所述，这些观察结果比较和对比了常规和信息素刺激的白色念珠菌生物膜形成的调节，并证明Cph1是后者所必需的，而不是前者。白色念珠菌是困扰人类的主要真菌病原体，许多感染是由于其容易形成生物膜而发生的。生物膜是复杂的多细胞群落，其中的细胞表现出与悬浮培养细胞不同的特性。它们在设备相关感染的发展中特别相关，因此了解生物膜调节和生物膜结构是优先事项。白念珠菌在不同的环境条件下具有形成不同类型生物膜的能力。在这里，我们比较了传统生物膜和信息素刺激的生物膜的形成规律，传统生物膜最近被发现有一个核心转录网络，信息素刺激的生物膜是当白色念珠菌的白细胞接触信息素时发生的。我们的研究表明，在这两种条件下，有几个调控成分控制着生物膜的形成，包括网络转录调控因子Bcr1、BRG1、Rob1和Tec1。然而，其他转录调控因子是每种生物膜发育模式特有的。特别是，我们证明了Cph1，交配过程中信息素反应的主要调节者，对于信息素刺激的生物膜的形成是必不可少的，但对于传统的生物膜是必不可少的。这些研究深入分析了信息素刺激的生物膜的调节，并证明了共同和独特的成分在这种人类病原体的生物膜形成的不同模式中起作用。
Candida albicans can stochastically switch between two phenotypes, white and opaque. Opaque cells are the sexually competent form of C. albicans and therefore undergo efficient polarized growth and mating in the presence of pheromone. In contrast, white cells cannot mate, but are induced – under a specialized set of conditions – to form biofilms in response to pheromone. In this work, we compare the genetic regulation of such “pheromone-stimulated” biofilms with that of “conventional” C. albicans biofilms. In particular, we examined a network of six transcriptional regulators (Bcr1, Brg1, Efg1, Tec1, Ndt80, and Rob1) that mediate conventional biofilm formation for their potential roles in pheromone-stimulated biofilm formation. We show that four of the six transcription factors (Bcr1, Brg1, Rob1, and Tec1) promote formation of both conventional and pheromone-stimulated biofilms, indicating they play general roles in cell cohesion and biofilm development. In addition, we identify the master transcriptional regulator of pheromone-stimulated biofilms as C. albicans Cph1, ortholog of Saccharomyces cerevisiae Ste12. Cph1 regulates mating in C. albicans opaque cells, and here we show that Cph1 is also essential for pheromone-stimulated biofilm formation in white cells. In contrast, Cph1 is dispensable for the formation of conventional biofilms. The regulation of pheromone- stimulated biofilm formation was further investigated by transcriptional profiling and genetic analyses. These studies identified 196 genes that are induced by pheromone signaling during biofilm formation. One of these genes, HGC1, is shown to be required for both conventional and pheromone-stimulated biofilm formation. Taken together, these observations compare and contrast the regulation of conventional and pheromone-stimulated biofilm formation in C. albicans, and demonstrate that Cph1 is required for the latter, but not the former. Candida albicans is the predominant fungal pathogen afflicting humans, where many infections arise due to its proclivity to form biofilms. Biofilms are complex multicellular communities in which cells exhibit distinct properties to those grown in suspension. They are particularly relevant in the development of device-associated infections, and thus understanding biofilm regulation and biofilm architecture is a priority. C. albicans has the ability to form different types of biofilms under different environmental conditions. Here, we compare the regulation of biofilm formation in conventional biofilms, for which a core transcriptional network has recently been identified, with pheromone-stimulated biofilms, which occur when C. albicans white cells are exposed to pheromone. Our studies show that several regulatory components control biofilm formation under both conditions, including the network transcriptional regulators Bcr1, Brg1, Rob1, and Tec1. However, other transcriptional regulators are specific to each model of biofilm development. In particular, we demonstrate that Cph1, the master regulator of the pheromone response during mating, is essential for pheromone-stimulated biofilm formation but is dispensable for conventional biofilms. These studies provide an in-depth analysis of the regulation of pheromone-stimulated biofilms, and demonstrate that both shared and unique components operate in different models of biofilm formation in this human pathogen.
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影响因子：
64.5
作者：
Chou, S;Huang, L;Liu, HP
通讯作者：
Liu, HP
影响因子：
10.5
作者：
ERREDE, B;AMMERER, G
通讯作者：
AMMERER, G
影响因子：
3.6
作者：
Bennett, Richard J.;Johnson, Alexander D.
通讯作者：
Johnson, Alexander D.
DOI：
10.1073/pnas.0605270103
发表时间：
2006-08-22
影响因子：
11.1
作者：
Huang, Guanghua;Wang, Huafeng;Liu, Haoping
通讯作者：
Liu, Haoping
影响因子：
3.1
作者：
BEDELL, GW;SOLL, DR
通讯作者：
SOLL, DR