Aspergillus fumigatus Raw sequence reads. Aspergillus fumigatus

The opportunistic pathogen Aspergillus fumigatus is found on all continents, and thrives in soil and agricultural environments. Its ability to readily adapt to novel environments and to produce billions of spores led to the spread of azole-resistant A. fumigatus across the globe, posing a threat to many immunocompromised patients, including critically-ill patients with severe influenza or COVID-19. In our study we sought to compare the adaptational response to azoles from A. fumigatus isolates that differ in azole susceptibility and genetic background. To gain more insight in how short-term adaptation to stressful azole compounds is managed through gene expression, we conducted an RNA-seq study on the response of A. fumigatus to itraconazole and the newest clinically approved azole, isavuconazole. We observed many similarities in ergosterol biosynthesis up-regulation across isolates with the exception of the pan-azole resistant isolate, which showed very little differential regulation in comparison to other isolates. Additionally, we found differential regulation of membrane efflux transporters, secondary metabolites, iron metabolism, and various stress-response and cell signaling mechanisms.

机会致病性致病菌烟曲霉（Aspergillus fumigatus）遍布全球各大洲，可在土壤与农业环境中旺盛生长。其易于适应全新环境并可产生数十亿孢子的特性，使得耐唑类（azole）烟曲霉菌株在全球范围内扩散，对众多免疫功能低下患者构成严重威胁，其中包括罹患重症流感或新型冠状病毒肺炎（COVID-19）的危重症患者。本研究旨在对比不同唑类敏感性与遗传背景的烟曲霉分离株对唑类的适应性应答反应。为深入解析烟曲霉如何通过基因表达实现对唑类应激化合物的短期适应性调控机制，本研究开展了RNA测序（RNA-seq）实验，以探究烟曲霉对伊曲康唑（itraconazole）以及最新临床获批的唑类药物艾沙康唑（isavuconazole）的应答特征。我们观察到，除泛唑类耐药分离株外，其余各分离株在麦角固醇生物合成通路上调方面存在诸多共性；而该泛唑类耐药分离株与其他分离株相比，仅表现出极微弱的差异表达调控。此外，我们还发现膜外排转运蛋白、次级代谢产物、铁代谢以及各类应激应答与细胞信号传导机制均存在差异表达调控。