A genome-wide transcriptional analysis of morphology determination in Candida albicans
A genome-wide transcriptional analysis of morphology determination in Candida albicans
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DOI：
10.1091/mbc.e12-01-0065
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发表时间：
2013-02-01
影响因子：
3.3
通讯作者：
Kadosh, David
中科院分区：
文献类型：
--
作者：
Carlisle, Patricia L.;Kadosh, David
白色念珠菌是人类真菌感染的最常见原因，它经历了从酵母到假菌丝和菌丝的可逆形态转变，这是毒力所必需的。多年来，与确定特定白念珠菌形态相关的全球基因表达模式之间的关系一直模糊不清。使用一株可以在没有复杂的环境线索和上游信号通路的情况下通过基因操作从酵母到伪菌丝再到菌丝的菌株，我们通过全基因组转录图谱证明，与伪菌丝相关的基因代表与菌丝相关的基因的子集，通常在较低水平表达。我们的结果也有力地表明，除了剂量，细丝特异基因表达的延长持续时间足以驱动白色念珠菌酵母-假菌丝-菌丝的转变。最后，我们描述了白念珠菌反向菌丝-假菌丝-酵母转变的第一个转录图谱，并证明这种转变不仅涉及已知的菌丝特异基因的下调，而且还涉及以前与正向转变相关的其他基因的差异表达，包括许多参与蛋白质合成的基因。这些发现为确定真菌形态重要的全基因组表达模式提供了新的见解，并表明除了相似之处外，随着病原丝状真菌经历正向和反向形态转变，全球基因表达也存在根本差异。
Candida albicans, the most common cause of human fungal infections, undergoes a reversible morphological transition from yeast to pseudohyphal and hyphal filaments, which is required for virulence. For many years, the relationship among global gene expression patterns associated with determination of specific C. albicans morphologies has remained obscure. Using a strain that can be genetically manipulated to sequentially transition from yeast to pseudohyphae to hyphae in the absence of complex environmental cues and upstream signaling pathways, we demonstrate by whole-genome transcriptional profiling that genes associated with pseudohyphae represent a subset of those associated with hyphae and are generally expressed at lower levels. Our results also strongly suggest that in addition to dosage, extended duration of filament-specific gene expression is sufficient to drive the C. albicans yeast-pseudohyphal-hyphal transition. Finally, we describe the first transcriptional profile of the C. albicans reverse hyphal-pseudohyphal-yeast transition and demonstrate that this transition involves not only down-regulation of known hyphal-specific, genes but also differential expression of additional genes that have not previously been associated with the forward transition, including many involved in protein synthesis. These findings provide new insight into genome-wide expression patterns important for determining fungal morphology and suggest that in addition to similarities, there are also fundamental differences in global gene expression as pathogenic filamentous fungi undergo forward and reverse morphological transitions.