Abstract：
Introduction. The fungal pathogen Aspergillus fumigatus can induce prolonged colonization of the lungs of susceptible patients, resulting in conditions such as allergic bronchopulmonary aspergillosis and chronic pulmonary aspergillosis.Hypothesis. Analysis of the A. fumigatus secretome released during sub-lethal infection of G. mellonella larvae may give an insight into products released during prolonged human colonisation.Methodology. Galleria mellonella larvae were infected with A. fumigatus, and the metabolism of host carbohydrate and proteins and production of fungal virulence factors were analysed. Label-free qualitative proteomic analysis was performed to identify fungal proteins in larvae at 96 hours post-infection and also to identify changes in the Galleria proteome as a result of infection.Results. Infected larvae demonstrated increasing concentrations of gliotoxin and siderophore and displayed reduced amounts of haemolymph carbohydrate and protein. Fungal proteins (399) were detected by qualitative proteomic analysis in cell-free haemolymph at 96 hours and could be categorized into seven groups, including virulence (n = 25), stress response (n = 34), DNA repair and replication (n = 39), translation (n = 22), metabolism (n = 42), released intracellular (n = 28) and cellular development and cell cycle (n = 53). Analysis of the Gallerial proteome at 96 hours post-infection revealed changes in the abundance of proteins associated with immune function, metabolism, cellular structure, insect development, transcription/translation and detoxification.Conclusion. Characterizing the impact of the fungal secretome on the host may provide an insight into how A. fumigatus damages tissue and suppresses the immune response during long-term pulmonary colonization.
摘要：
Introduction.真菌病原体烟曲霉可诱导易感患者肺部长期定植，导致过敏性支气管肺曲霉病和慢性肺曲霉病等疾病。假说。对亚致死性G.mellonella幼虫感染过程中释放的烟曲霉分泌组的分析可能会提供对长期人类定殖过程中释放的产物的见解。方法论。Galleriamellonella幼虫被烟曲霉感染，并分析了宿主碳水化合物和蛋白质的代谢以及真菌毒力因子的产生。进行无标记的定性蛋白质组分析以鉴定感染后96小时幼虫中的真菌蛋白,并且还鉴定作为感染结果的Galleria蛋白质组的变化。结果。感染的幼虫显示出胶质毒素和铁载体的浓度增加，并且血淋巴碳水化合物和蛋白质的含量减少。在96小时的无细胞血淋巴中通过定性蛋白质组学分析检测到真菌蛋白（399），可分为7组，包括毒力（n=25），应激反应(n=34)，DNA修复和复制（n=39），翻译（n=22），新陈代谢（n=42），释放细胞内（n=28）和细胞发育和细胞周期（n=53）。感染后96小时的Gallerial蛋白质组分析显示，与免疫功能相关的蛋白质丰度发生变化，新陈代谢，细胞结构，昆虫发育,转录/翻译和解毒。结论。表征真菌分泌组对宿主的影响可以提供关于烟曲霉如何在长期肺部定植期间损伤组织和抑制免疫应答的见解。
