Global Transcriptome Changes Underlying Colony Growth in the Opportunistic Human Pathogen Aspergillus fumigatus
Global Transcriptome Changes Underlying Colony Growth in the Opportunistic Human Pathogen Aspergillus fumigatus
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DOI：
10.1128/ec.05102-11
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发表时间：
2012-01-01
期刊：
影响因子：
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通讯作者：
Rokas, Antonis
中科院分区：
文献类型：
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作者：
Gibbons, John G.;Beauvais, Anne;Rokas, Antonis
烟曲霉菌是世界范围内最常见和最致命的肺部真菌感染。在肺中，真菌通常形成密集的丝状菌落，嵌在聚合的细胞外基质中。为了确定参与这种生物膜（BF）生长的候选基因，我们使用RNA-Seq比较BF和液体浮游生物（PL）生长的转录组。针对A.烟曲霉转录组鉴定了3，728个在两种条件下差异调节的基因。虽然这些基因中的许多，包括编码转录因子，应激反应，核糖体和翻译机制的基因，可能反映了两种条件下不同的生长需求，但我们的实验还确定了数百个候选基因，用于观察BF和PL之间的形态学和病理学差异。我们发现在运输，次生代谢，细胞壁和表面功能的上调基因的过度表达。此外，上调的基因在A.烟曲霉基因组;它们更可能发生在亚端粒区域，并共定位在27个基因组邻域中，其中许多与已知或候选的次生代谢基因簇重叠。我们还发现了1,164个下调的基因。该基因组在基因组中没有空间结构，并且在参与主要代谢功能（包括碳和氨基酸代谢）的基因中过度表达。这些结果增加了有价值的洞察生物膜形成的遗传学在A。fumigatus和其它丝状真菌，并在生物膜生物学的背景下鉴定许多相关的候选基因用于下游功能实验。
Aspergillus fumigatus is the most common and deadly pulmonary fungal infection worldwide. In the lung, the fungus usually forms a dense colony of filaments embedded in a polymeric extracellular matrix. To identify candidate genes involved in this biofilm (BF) growth, we used RNA-Seq to compare the transcriptomes of BF and liquid plankton (PL) growth. Sequencing and mapping of tens of millions sequence reads against the A. fumigatus transcriptome identified 3,728 differentially regulated genes in the two conditions. Although many of these genes, including the ones coding for transcription factors, stress response, the ribosome, and the translation machinery, likely reflect the different growth demands in the two conditions, our experiment also identified hundreds of candidate genes for the observed differences in morphology and pathobiology between BF and PL. We found an overrepresentation of upregulated genes in transport, secondary metabolism, and cell wall and surface functions. Furthermore, upregulated genes showed significant spatial structure across the A. fumigatus genome; they were more likely to occur in subtelomeric regions and colocalized in 27 genomic neighborhoods, many of which overlapped with known or candidate secondary metabolism gene clusters. We also identified 1,164 genes that were downregulated. This gene set was not spatially structured across the genome and was overrepresented in genes participating in primary metabolic functions, including carbon and amino acid metabolism. These results add valuable insight into the genetics of biofilm formation in A. fumigatus and other filamentous fungi and identify many relevant, in the context of biofilm biology, candidate genes for downstream functional experiments.