Hyphal development in Candida albicans from different cell states
Hyphal development in Candida albicans from different cell states
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不同细胞状态的白色念珠菌的菌丝发育
DOI：
10.1007/s00294-018-0845-5
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发表时间：
2018
期刊：
影响因子：
2.5
通讯作者：
Lu Yang
中科院分区：
文献类型：
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作者：
Su Chang;Yu jing;Lu Yang
白色念珠菌是免疫功能低下个体的重要机会性真菌病原体。在酵母、假菌丝和菌丝生长形式之间切换的能力（多态性）是白色念珠菌研究最多的毒力属性之一。实验室中诱导菌丝形成的常用方法是将饱和培养物中的细胞稀释到 37°C 的新鲜培养基中。先前已研究过这些条件下作用的分子机制。白色念珠菌无需稀释也可以在生长的细胞中形成菌丝。白色念珠菌在不同细胞状态下形成菌丝的能力有助于真菌在感染过程中适应不同的宿主环境。 Su 等人最近的一项研究。揭示了白色念珠菌在不接种条件下形成菌丝的分子机制。 N-乙酰氨基葡萄糖 (GlcNAc) 通过下调 NRG1（菌丝发育的主要抑制因子）的转录来刺激对数期细胞的丝状形成。 GlcNAc 传感器 Ngs1 负责此过程，而不是 cAMP-PKA 途径。 Ngs1 与 GlcNAc 结合，激活其 N-乙酰转移酶活性，从而诱导 BRG1 表达。 BRG1 水平的增加可以抑制 NRG1 转录，导致菌丝生长。血清或中性 pH 诱导的对数期细胞中的菌丝发育也需要激活 BRG1 以下调 NRG1 转录。因此，在不接种的条件下，菌丝诱导是由 Brg1 介导的 Nrg1 抑制消除触发的。这篇综述描述了我们目前对菌丝发育分子机制的理解，菌丝发育是白色念珠菌中研究最充分的毒力因子。这些将扩大潜在药物靶点的数量，并提供新的抗毒力治疗作用模式。
Candida albicans is an important opportunistic fungal pathogen of immunocompromised individuals. The ability to switch between yeast, pseudohyphal, and hyphal growth forms (polymorphism) is one of the most investigated virulence attributes of C. albicans. The usual method for inducing hypha formation in the lab is by diluting cells from a saturated culture into fresh medium at 37 °C. The molecular mechanism at action under these conditions has been previously investigated. C. albicans can also form hyphae in growing cells without dilution. The ability of C. albicans to form hyphae in different cell states facilitates the fungus to adapt varied host environments during infection. A recent study by Su et al. uncovered the molecular mechanism for how C. albicans develops hyphae under the condition without inoculation. N-Acetylglucosamine (GlcNAc) stimulates filamentation in log phase cells through transcriptional down-regulation of NRG1, the major repressor of hyphal development. Instead of cAMP–PKA pathway, GlcNAc sensor Ngs1 is responsible for this process. Ngs1 binds to GlcNAc to activate its N-acetyltransferase activity, leading to the induction of BRG1 expression. The increased level of BRG1 could repress NRG1 transcripts, resulting in hyphal growth. Hyphal development in log phase cells induced by serum or neutral pH also requires activation of BRG1 to down-regulate NRG1 transcription. Therefore, hyphal induction under the condition without inoculation is trigged by Brg1-mediated removal of Nrg1 inhibition. This review describes our current understanding of the molecular mechanism underlying hyphal development, the best studied virulence factor in C. albicans. These will expand the number of potential drug targets with novel modes of action for anti-virulence therapeutics.