Transcriptomic and proteomic analyses of the Aspergillus fumigatus hypoxia response using an oxygen-controlled fermenter.
Transcriptomic and proteomic analyses of the Aspergillus fumigatus hypoxia response using an oxygen-controlled fermenter.
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DOI：
10.1186/1471-2164-13-62
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发表时间：
2012-02-06
期刊：
影响因子：
4.4
通讯作者：
Cramer RA
中科院分区：
文献类型：
--
作者：
Barker BM;Kroll K;Vödisch M;Mazurie A;Kniemeyer O;Cramer RA
烟曲霉菌是一种霉菌，导致人类大多数曲霉病病例。为了在人体内生存，A。烟曲霉必须适应通常以低养分和氧气可用性为特征的微环境。最近的研究表明，A.烟曲霉等病原真菌对缺氧的适应有助于其毒力的提高。然而，A.烟曲霉低氧适应知之甚少。为了更好地理解A。为了研究烟曲霉对人体真菌致病过程中体内缺氧微环境的适应性，利用控氧发酵罐系统研究了缺氧条件下烟曲霉转录组和蛋白质组的动态变化。与铁和固醇代谢，细胞壁，GABA分流，和转录调节相关的转录显着增加，观察到在响应缺氧。核糖体和萜类骨架生物合成，TCA循环，氨基酸代谢和RNA降解的转录本中观察到的伴随减少。转录因子mRNA丰度的变化分析表明，缺氧诱导显着的积极和消极的变化，可能是重要的调节缺氧反应，在这种致病性霉菌。缺氧生长导致几种糖酵解酶蛋白水平的变化，但这些变化并不总是反映了相应的转录谱数据。然而，对于所有时间点，转录组学和蛋白质组学数据集之间总体上存在良好的相关性（R2 = 0.2，p < 0.05）。一些转录水平和随后的蛋白水平之间缺乏相关性，提示了A.烟熏。综上所述，我们的数据表明，一个强大的细胞反应，可能是调节在转录和转录后水平，以响应缺氧的人致病性霉菌A。烟熏。与其他致病真菌一样，糖酵解的诱导和TCA循环的转录下调以及氧化磷酸化似乎是这种致病霉菌中缺氧反应的主要组成部分。此外，一个显着的诱导的转录参与麦角固醇生物合成是一致的，与以前的观察结果，在致病性酵母菌白色念珠菌和新型隐球菌，表明保守的这种反应，在致病性真菌缺氧。因为麦角固醇生物合成酶也需要铁作为辅因子，铁摄取转录物的增加与缺氧条件下对铁的需求增加一致。然而，与C.白色念珠菌和C.在新生儿中，GABA分流似乎在降低缺氧时A.这将是有趣的，以确定这是否是真菌毒力的关键。总体而言，A.烟曲霉缺氧反应似乎涉及转录和蛋白质水平的转录和转录后控制，因此为将来分析它们在缺氧适应和真菌毒力中的作用提供了候选基因。
Aspergillus fumigatus is a mold responsible for the majority of cases of aspergillosis in humans. To survive in the human body, A. fumigatus must adapt to microenvironments that are often characterized by low nutrient and oxygen availability. Recent research suggests that the ability of A. fumigatus and other pathogenic fungi to adapt to hypoxia contributes to their virulence. However, molecular mechanisms of A. fumigatus hypoxia adaptation are poorly understood. Thus, to better understand how A. fumigatus adapts to hypoxic microenvironments found in vivo during human fungal pathogenesis, the dynamic changes of the fungal transcriptome and proteome in hypoxia were investigated over a period of 24 hours utilizing an oxygen-controlled fermenter system. Significant increases in transcripts associated with iron and sterol metabolism, the cell wall, the GABA shunt, and transcriptional regulators were observed in response to hypoxia. A concomitant reduction in transcripts was observed with ribosome and terpenoid backbone biosynthesis, TCA cycle, amino acid metabolism and RNA degradation. Analysis of changes in transcription factor mRNA abundance shows that hypoxia induces significant positive and negative changes that may be important for regulating the hypoxia response in this pathogenic mold. Growth in hypoxia resulted in changes in the protein levels of several glycolytic enzymes, but these changes were not always reflected by the corresponding transcriptional profiling data. However, a good correlation overall (R2 = 0.2, p < 0.05) existed between the transcriptomic and proteomics datasets for all time points. The lack of correlation between some transcript levels and their subsequent protein levels suggests another regulatory layer of the hypoxia response in A. fumigatus. Taken together, our data suggest a robust cellular response that is likely regulated both at the transcriptional and post-transcriptional level in response to hypoxia by the human pathogenic mold A. fumigatus. As with other pathogenic fungi, the induction of glycolysis and transcriptional down-regulation of the TCA cycle and oxidative phosphorylation appear to major components of the hypoxia response in this pathogenic mold. In addition, a significant induction of the transcripts involved in ergosterol biosynthesis is consistent with previous observations in the pathogenic yeasts Candida albicans and Cryptococcus neoformans indicating conservation of this response to hypoxia in pathogenic fungi. Because ergosterol biosynthesis enzymes also require iron as a co-factor, the increase in iron uptake transcripts is consistent with an increased need for iron under hypoxia. However, unlike C. albicans and C. neoformans, the GABA shunt appears to play an important role in reducing NADH levels in response to hypoxia in A. fumigatus and it will be intriguing to determine whether this is critical for fungal virulence. Overall, regulatory mechanisms of the A. fumigatus hypoxia response appear to involve both transcriptional and post-transcriptional control of transcript and protein levels and thus provide candidate genes for future analysis of their role in hypoxia adaptation and fungal virulence.
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影响因子：
4.3
作者：
Eden E;Lipson D;Yogev S;Yakhini Z
通讯作者：
Yakhini Z
影响因子：
4.8
作者：
Coleman, ST;Fang, TK;Moye-Rowley, WS
通讯作者：
Moye-Rowley, WS
影响因子：
3.7
作者：
Boelte KC;Gordy LE;Joyce S;Thompson MA;Yang L;Lin PC
通讯作者：
Lin PC
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
3.3
作者：
Davies, Brandon S. J.;Rine, Jasper
通讯作者：
Rine, Jasper