Hyphal induction under the condition without inoculation in Candida albicans is triggered by Brg1-mediated removal of NRG1 inhibition
Hyphal induction under the condition without inoculation in Candida albicans is triggered by Brg1-mediated removal of NRG1 inhibition
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白色念珠菌在未接种条件下的菌丝诱导是由 Brg1 介导的 NRG1 抑制消除触发的
DOI：
10.1111/mmi.13944
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发表时间：
2018
影响因子：
3.6
通讯作者：
Lu Yang
中科院分区：
文献类型：
--
作者：
Su Chang;Yu Jing;Sun Qiangqiang;Liu Qian;Lu Yang
白色念珠菌可以在酵母和菌丝生长形态之间切换，这是其发病机制的关键。常规的方法是在37℃下从饱和细胞中稀释到新鲜的培养液中诱导菌丝，这依赖于cAMP-PKA途径激活的NRG1转录下调和Nrg1蛋白的降解。据报道，N-乙酰氨基葡萄糖(GlcNAc)、血清或中性pH均可刺激对数生长期细胞的丝状化，而HowC。白念珠菌在没有接种的情况下会产生菌丝，目前尚不清楚。在这里，我们证明了在这种条件下，NRG1下调对于菌丝生长是必要的。GlcNAc传感器Ngs1不是cAMP-PKA途径，而是通过其N-乙酰转移酶活性下调对数期细胞中GlcNAc诱导的NRG1的表达。从基因筛查中发现，BRG1对于菌丝的发育是必不可少的，而不需要接种。NGS1与BRG1启动子结合，诱导其在GlcNAc中表达。重要的是，结构性表达的BRG1即使在没有GlcNAc或NGS1的情况下也会诱导NRG1下调。血清或中性pH诱导对数期细胞的丝状化也是通过BRG1介导的NRG1下调。我们的研究为HowC提供了一种分子机制。白念珠菌在不同的细胞状态下转化菌丝。这种灵活性可能有助于C。白念珠菌在感染过程中适应不同的寄主环境。
Candida albicanscan switch between yeast and hyphae growth forms, which is critical for its pathogenesis. Diluting from saturated cells into fresh medium at 37°C is routinely used to induce hyphae, which depends on the cAMP‐PKA pathway‐activated transcriptional down‐regulation ofNRG1and degradation of Nrg1 protein triggered by inoculation. It is reported that N‐acetylglucosamine (GlcNAc), serum or neutral pH could stimulate filamentation in log phase cells, whereas howC. albicansdevelops hyphae without inoculation remains unknown. Here, we show thatNRG1down‐regulation is necessary for hyphal growth under this condition. Instead of cAMP‐PKA pathway, GlcNAc sensor Ngs1 is responsible for the down‐regulation ofNRG1upon GlcNAc induction in log phase cells through itsN‐acetyltransferase activity. From a genetic screen, Brg1 is found to be essential for hyphal development without inoculation. Ngs1 binds toBRG1promoter to induce its expression in GlcNAc. Importantly, constitutively expressedBRG1inducesNRG1down‐regulation even in the absence of GlcNAc or Ngs1. Serum or neutral pH‐induced filamentation in log phase cells is also through Brg1‐mediatedNRG1down‐regulation. Our study provides a molecular mechanism for howC. albicansforms hyphae in different cell states. This flexibility may facilitateC. albicansto adapt varied host environment during infection.