N-Acetylglucosamine-Induced Cell Death in Candida albicans and Its Implications for Adaptive Mechanisms of Nutrient Sensing in Yeasts.
N-Acetylglucosamine-Induced Cell Death in Candida albicans and Its Implications for Adaptive Mechanisms of Nutrient Sensing in Yeasts.
复制标题
N-乙酰氨基葡萄糖诱导的白色念珠菌细胞死亡及其对酵母营养感应适应性机制的影响。
DOI：
10.1128/mbio.01376-15
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发表时间：
2015-09-08
期刊：
影响因子：
6.4
通讯作者：
Huang G
中科院分区：
文献类型：
--
作者：
Du H;Guan G;Li X;Gulati M;Tao L;Cao C;Johnson AD;Nobile CJ;Huang G
单细胞生物在不断变化的环境中具有不同的感知和利用营养物质的策略。机会性真菌病原体白色念珠菌是人类微生物群的常见成员，尤其是胃肠道 (GI) 微生物群。一个重要的问题涉及白色念珠菌如何获得相对于其他微生物的竞争优势，成为成功的共生和机会致病菌。在这里，我们报告白色念珠菌使用 N-乙酰氨基葡萄糖 (GlcNAc)（胃肠道中存在的丰富碳源）作为营养可用性的信号。当放入水中时，白色念珠菌细胞通常会进入 G0 期并保持活力数周。然而，当在仅含有 GlcNAc 的水中培养时，它们很快就会失去活力。我们将这种现象称为 GlcNAc 诱导的细胞死亡 (GICD)。 GlcNAc 触发核糖体生物发生基因的上调、线粒体代谢的改变以及活性氧 (ROS) 的积累，然后通过细胞凋亡和坏死机制导致细胞快速死亡。 GICD 涉及多种途径，包括保守的环 AMP (cAMP) 信号传导和 GlcNAc 分解代谢途径。 GlcNAc 作为信号分子以协调的方式调节多个细胞程序，从而最大限度地提高营养物质的利用效率。这种适应性行为使白色念珠菌能够更有效地在肠道定植。对环境中营养物质快速、适当反应的能力对于自由生活的微生物至关重要。为了最大限度地利用可用营养物质，微生物通常使用限制性营养成分作为信号来协调多个生物过程。人类真菌病原体白色念珠菌使用 N-乙酰氨基葡萄糖 (GlcNAc) 作为外部营养资源可用性的信号。由于氧化代谢的组成性激活和活性氧 (ROS) 的积累，GlcNAc 会诱导白色念珠菌快速细胞死亡，并且多种途径参与其调节。这项研究揭示了病原真菌生态位特化的机制，并提出了这种细胞死亡途径可能成为尚未探索的治疗靶点的可能性。
Single-celled organisms have different strategies to sense and utilize nutrients in their ever-changing environments. The opportunistic fungal pathogen Candida albicans is a common member of the human microbiota, especially that of the gastrointestinal (GI) tract. An important question concerns how C. albicans gained a competitive advantage over other microbes to become a successful commensal and opportunistic pathogen. Here, we report that C. albicans uses N-acetylglucosamine (GlcNAc), an abundant carbon source present in the GI tract, as a signal for nutrient availability. When placed in water, C. albicans cells normally enter the G0 phase and remain viable for weeks. However, they quickly lose viability when cultured in water containing only GlcNAc. We term this phenomenon GlcNAc-induced cell death (GICD). GlcNAc triggers the upregulation of ribosomal biogenesis genes, alterations of mitochondrial metabolism, and the accumulation of reactive oxygen species (ROS), followed by rapid cell death via both apoptotic and necrotic mechanisms. Multiple pathways, including the conserved cyclic AMP (cAMP) signaling and GlcNAc catabolic pathways, are involved in GICD. GlcNAc acts as a signaling molecule to regulate multiple cellular programs in a coordinated manner and therefore maximizes the efficiency of nutrient use. This adaptive behavior allows C. albicans’ more efficient colonization of the gut. The ability to rapidly and appropriately respond to nutrients in the environment is crucial to free-living microorganisms. To maximize the use of available nutrients, microorganisms often use a limiting nutritional component as a signal to coordinate multiple biological processes. The human fungal pathogen Candida albicans uses N-acetylglucosamine (GlcNAc) as a signal for the availability of external nutrient resources. GlcNAc induces rapid cell death in C. albicans due to the constitutive activation of oxidative metabolism and accumulation of reactive oxygen species (ROS), and multiple pathways are involved in its regulation. This study sheds light on the mechanisms of niche specialization of pathogenic fungi and raises the possibility that this cell death pathway could be an unexplored therapeutic target.