N-acetylglucosamine (GlcNAc) triggers a rapid, temperature-responsive morphogenetic program in thermally dimorphic fungi.
N-acetylglucosamine (GlcNAc) triggers a rapid, temperature-responsive morphogenetic program in thermally dimorphic fungi.
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DOI：
10.1371/journal.pgen.1003799
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发表时间：
2013
期刊：
影响因子：
4.5
通讯作者：
Sil A
中科院分区：
文献类型：
--
作者：
Gilmore SA;Naseem S;Konopka JB;Sil A
单糖N-乙酰葡糖胺（GlcNAc）是微生物细胞壁的主要成分，在环境中普遍存在。GlcNAc刺激真菌病原体白色念珠菌（Candida albicans）的发育途径，白色念珠菌是一种寄生在哺乳动物肠道中并在宿主免疫缺陷的情况下引起疾病的寄生生物。在这里，我们研究了GlcNAc信号在热二型人类真菌病原体，一组真菌，是高度进化分歧从C。白色念珠菌，甚至在健康个体中也引起疾病。这些土壤生物生长为极化的多细胞菌丝丝，当被人类宿主吸入时转变为单细胞致病酵母形式。温度是促进可逆细胞分化为酵母或丝状体的主要环境因素;然而，在体外向较低温度的转变以低效和异步的方式诱导丝状体生长。我们发现GlcNAc是一个有效的和特定的诱导剂的酵母丝的转变，在两个热二型真菌，荚膜组织胞浆菌和芽生菌dermativum。微摩尔浓度的GlcNAc不仅能增加丝状体的生长速率，还能诱导H.在温度变化后，荚膜中的GlcNAc不依赖于GlcNAc催化剂，表明真菌细胞感测GlcNAc以促进表达。全基因组表达谱分析，以确定参与建立丝状生长程序的候选基因，发现两个基因编码GlcNAc转运蛋白，NGT 1和NGT 2，这是必要的H。荚膜细胞响应于GlcNAc而强健地形成丝状体。出乎意料的是，NGT 1和NGT 2对于高效H.这表明Ngt 1和Ngt 2监测GlcNAc的内源性水平以控制响应于温度的多细胞丝状生长。总体而言，我们的工作表明，GlcNAc功能作为一个高度保守的线索，真菌的形态发生，这进一步增强了这种普遍存在的糖在真核生物中的细胞信号转导的意义。与大多数真菌病原体形成鲜明对比的是，热二型真菌病原体在免疫活性人中引起全身感染。热二型真菌在土壤中生长为多细胞丝状形式，专门用于在这个特定的环境生态位中复制。在感染人类后，这些真菌转变为适于在哺乳动物宿主内复制和致病的寄生细胞类型。在这项工作中，我们研究的因素是重要的传染性，环境形式的热二型真菌的生长。我们发现，N-乙酰葡糖胺（GlcNAc），一种普遍存在的碳水化合物，在所有生命领域中具有细胞作用，刺激两种热二型真菌病原体（荚膜组织胞浆菌和皮肤芽生菌）向环境形式的转换。分析真菌细胞如何响应GlcNAc揭示，这些真菌具有两个GlcNAc转运蛋白，这对于控制它们在感染和寄生状态之间切换的能力是重要的。总的来说，我们的工作开始阐明促进这些生物体以感染形式生长的途径，这对我们理解促进热二型真菌疾病传播的环境信号至关重要。
The monosaccharide N-acetylglucosamine (GlcNAc) is a major component of microbial cell walls and is ubiquitous in the environment. GlcNAc stimulates developmental pathways in the fungal pathogen Candida albicans, which is a commensal organism that colonizes the mammalian gut and causes disease in the setting of host immunodeficiency. Here we investigate GlcNAc signaling in thermally dimorphic human fungal pathogens, a group of fungi that are highly evolutionarily diverged from C. albicans and cause disease even in healthy individuals. These soil organisms grow as polarized, multicellular hyphal filaments that transition into a unicellular, pathogenic yeast form when inhaled by a human host. Temperature is the primary environmental cue that promotes reversible cellular differentiation into either yeast or filaments; however, a shift to a lower temperature in vitro induces filamentous growth in an inefficient and asynchronous manner. We found GlcNAc to be a potent and specific inducer of the yeast-to-filament transition in two thermally dimorphic fungi, Histoplasma capsulatum and Blastomyces dermatitidis. In addition to increasing the rate of filamentous growth, micromolar concentrations of GlcNAc induced a robust morphological transition of H. capsulatum after temperature shift that was independent of GlcNAc catabolism, indicating that fungal cells sense GlcNAc to promote filamentation. Whole-genome expression profiling to identify candidate genes involved in establishing the filamentous growth program uncovered two genes encoding GlcNAc transporters, NGT1 and NGT2, that were necessary for H. capsulatum cells to robustly filament in response to GlcNAc. Unexpectedly, NGT1 and NGT2 were important for efficient H. capsulatum yeast-to-filament conversion in standard glucose medium, suggesting that Ngt1 and Ngt2 monitor endogenous levels of GlcNAc to control multicellular filamentous growth in response to temperature. Overall, our work indicates that GlcNAc functions as a highly conserved cue of morphogenesis in fungi, which further enhances the significance of this ubiquitous sugar in cellular signaling in eukaryotes. In stark contrast to most fungal pathogens, thermally dimorphic fungal pathogens cause systemic infections in immunocompetent humans. Thermally dimorphic fungi grow in the soil as a multicellular filamentous form specialized for replication in this particular environmental niche. Upon infection of a human, these fungi transition to a parasitic cell type that is adapted for replication and pathogenesis within a mammalian host. In this work, we examined factors that are important for growth of the infectious, environmental form of thermally dimorphic fungi. We discovered that N-acetylglucosamine (GlcNAc), a ubiquitous carbohydrate with cellular roles across all kingdoms of life, stimulated a switch to the environmental form for two thermally dimorphic fungal pathogens, Histoplasma capsulatum and Blastomyces dermatitidis. Analysis of how fungal cells respond to GlcNAc revealed that these fungi possess two GlcNAc transporters that are important for controlling their ability to switch between infectious and parasitic states. Overall, our work begins to elucidate the pathways that promote growth in the infectious form of these organisms, which is critical to our understanding of environmental signals that promote disease transmission of thermally dimorphic fungi.
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影响因子：
64.5
作者：
Dennis JW;Nabi IR;Demetriou M
通讯作者：
Demetriou M
影响因子：
3.6
作者：
Boyce, Kylie J.;Schreider, Lena;Andrianopoulos, Alex
通讯作者：
Andrianopoulos, Alex
影响因子：
4.3
作者：
Banerjee, Sulagna;Robbins, Phillips W.;Samuelson, John
通讯作者：
Samuelson, John
影响因子：
16.6
作者：
Hart GW;Slawson C;Ramirez-Correa G;Lagerlof O
通讯作者：
Lagerlof O
DOI：
10.1073/pnas.93.9.3870
发表时间：
1996-04-30
影响因子：
11.1
作者：
Carratu, L;Franceschelli, S;Maresca, B
通讯作者：
Maresca, B