Candida albicans ferric reductases are differentially regulated in response to distinct forms of iron limitation by the Rim101 and CBF transcription factors
Candida albicans ferric reductases are differentially regulated in response to distinct forms of iron limitation by the Rim101 and CBF transcription factors
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DOI：
10.1128/ec.00108-08
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发表时间：
2008-07-01
期刊：
影响因子：
--
通讯作者：
Davis, Dana A.
中科院分区：
文献类型：
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作者：
Baek, Yong-Un;Li, Mingchun;Davis, Dana A.
铁是一种必需的营养物质，在哺乳动物宿主体内受到严重限制。白色念珠菌编码一个由15个铁还原酶组成的家族，这是铁获取和利用所必需的。尽管铁还原酶在铁获取和动员中的核心作用，但对白色念珠菌中铁还原酶基因表达的调控网络知之甚少。在这里，我们已经证明了两种铁还原酶FRE2和FRP1的差异调控，以响应不同的铁限制环境。FRE2和FRP1都是由Rim101转录因子直接在碱性- ph环境中诱导的。然而，铁螯合也会诱导FRP1，而不是FRE2。我们已经确定了一个CCAAT基序作为螯合剂介导诱导的关键调控序列，并发现CCAAT结合因子（CBF）对于铁限制环境中FRP1的表达至关重要。我们发现，破坏CBF核心DNA结合活性的hap5 Delta/hap5 Delta突变体在铁限制条件下无法生长。白念珠菌编码三种cbf依赖性转录因子，我们确定了Hap43蛋白是铁限制反应所需的cbf依赖性转录因子。这些研究为真菌病原体白色念珠菌中铁还原酶基因表达的调控提供了关键的见解。
Iron is an essential nutrient that is severely limited in the mammalian host. Candida albicans encodes a family of 15 putative ferric reductases, which are required for iron acquisition and utilization. Despite the central role of ferric reductases in iron acquisition and mobilization, relatively little is known about the regulatory networks that govern ferric reductase gene expression in C. albicans. Here we have demonstrated the differential regulation of two ferric reductases, FRE2 and FRP1, in response to distinct iron-limited environments. FRE2 and FRP1 are both induced in alkaline-pH environments directly by the Rim101 transcription factor. However, FRP1 but not FRE2 is also induced by iron chelation. We have identified a CCAAT motif as the critical regulatory sequence for chelator-mediated induction and have found that the CCAAT binding factor (CBF) is essential for FRP1 expression in iron-limited environments. We found that a hap5 Delta/hap5 Delta mutant, which disrupts the core DNA binding activity of CBF, is unable to grow under iron-limited conditions. C. albicans encodes three CBF-dependent transcription factors, and we identified the Hap43 protein as the CBF-dependent transcription factor required for iron-limited responses. These studies provide key insights into the regulation of ferric reductase gene expression in the fungal pathogen C. albicans.