Portrait of <em>Candida albicans</em> Adherence Regulators

Cell-substrate adherence is a fundamental property of microorganisms that enables them to exist in biofilms. Our study focuses on adherence of the fungal pathogen Candida albicans to one substrate, silicone, that is relevant to device-associated infection. We conducted a mutant screen with a quantitative flow-cell assay to identify thirty transcription factors that are required for adherence. We then combined nanoString gene expression profiling with functional analysis to elucidate relationships among these transcription factors, with two major goals: to extend our understanding of transcription factors previously known to govern adherence or biofilm formation, and to gain insight into the many transcription factors we identified that were relatively uncharacterized, particularly in the context of adherence or cell surface biogenesis. With regard to the first goal, we have discovered a role for biofilm regulator Bcr1 in adherence, and found that biofilm regulator Ace2 is a major functional target of chromatin remodeling factor Snf5. In addition, Bcr1 and Ace2 share several target genes, pointing to a new connection between them. With regard to the second goal, our findings reveal existence of a large regulatory network that connects eleven adherence regulators, the zinc-response regulator Zap1, and approximately one quarter of the predicted cell surface protein genes in this organism. This limited yet sensitive glimpse of mutant gene expression changes had thus defined one of the broadest cell surface regulatory networks in C. albicans.细胞-底物黏附是微生物形成生物被膜（biofilms）的根本性特性。本研究聚焦于致病性真菌白色念珠菌（Candida albicans）与装置相关感染密切相关的底物硅酮（silicone）的黏附过程。我们通过定量流动池检测法（flow-cell assay）开展突变体筛选，成功鉴定出30个黏附所必需的转录因子（transcription factors）。随后，我们结合nanoString基因表达谱分析与功能实验，解析这些转录因子间的调控关联，本次研究设有两大核心目标：一是拓展我们对已知参与黏附或生物被膜形成的转录因子的认知，二是深入探究本次筛选中获得的大量功能未明的转录因子，尤其是其在黏附或细胞表面生物发生（cell surface biogenesis）过程中的作用。 针对第一个目标，我们发现生物被膜调控因子Bcr1在黏附过程中发挥了全新功能，同时证实生物被膜调控因子Ace2是染色质重塑因子（chromatin remodeling factor）Snf5的主要功能下游靶点。此外，Bcr1与Ace2共享多个靶基因，这揭示了二者间此前未被发现的调控联系。 针对第二个目标，我们的研究结果表明存在一个庞大的调控网络，该网络连接了11个黏附调控因子、锌应答调控因子（zinc-response regulator）Zap1，以及该菌种中约四分之一的预测细胞表面蛋白编码基因。本次针对突变体基因表达变化的有限但高灵敏度的分析，由此界定了白色念珠菌中覆盖范围最广的细胞表面调控网络之一。