1Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
2Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Microb Genom. 2018 Feb;4(2). doi: 10.1099/mgen.0.000154. Epub 2018 Jan 18.
Aspergillus fumigatus is an opportunistic, ubiquitous, saprophytic mould that can cause severe allergic responses in atopic individuals as well as life-threatening infections in immunocompromised patients. A critical step in the establishment of infection is the invasion of airway epithelial cells by the inhaled fungi. Understanding how A. fumigatus senses and responds to airway cells is important to understand the pathogenesis of invasive pulmonary aspergillosis. Here, we analysed the transcriptomes of two commonly used clinical isolates, Af293 and CEA10, during infection of the A549 type II pneumocyte cell line in vitro. We focused our RNA-seq analysis on the core set of genes that are present in the genomes of the two strains. Our results suggest that: (a) A. fumigatus does not mount a conserved transcriptional response to airway epithelial cells in our in vitro model and (b) strain background and time spent in the tissue culture media have a greater impact on the transcriptome than the presence of host cells. Our analyses reveal both common and strain-specific transcriptional programmes that allow for the generation of hypotheses about gene function as it pertains to pathogenesis and the significant phenotypic heterogeneity that is observed among A. fumigatus isolates.
烟曲霉是一种机会性、无处不在的腐生真菌,可在特应性个体中引起严重过敏反应,并可在免疫功能低下的患者中引起危及生命的感染。感染的一个关键步骤是吸入的真菌侵袭气道上皮细胞。了解烟曲霉如何感知和响应气道细胞对于理解侵袭性肺曲霉病的发病机制很重要。在这里,我们分析了两种常用临床分离株 Af293 和 CEA10 在体外感染 A549 型 II 型肺细胞系时的转录组。我们的 RNA-seq 分析集中在这两个菌株基因组中存在的核心基因集上。我们的结果表明:(a)在我们的体外模型中,烟曲霉不会对气道上皮细胞产生保守的转录反应;(b)与宿主细胞的存在相比,菌株背景和在组织培养基中花费的时间对转录组的影响更大。我们的分析揭示了允许针对与发病机制相关的基因功能生成假设的共同和菌株特异性转录程序,以及在烟曲霉分离株中观察到的显著表型异质性。