Department of Pathology & Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0529, USA.
Med Mycol. 2011 Apr;49 Suppl 1:S101-6. doi: 10.3109/13693786.2010.497504. Epub 2010 Jul 7.
The ability of Aspergillus fumigatus to establish and maintain an infection requires a continuous supply of nutrients to fuel energy production and growth. Like other filamentous fungi, A. fumigatus acquires nutrients by absorption, a mode of nutrition that depends upon the secretion of extracellular hydrolases to degrade the complex organic polymers in host tissues into reduced forms of carbon and nitrogen. If the folding capacity of the endoplasmic reticulum (ER) is exceeded during periods of high secretory activity, a signaling pathway known as the unfolded protein response (UPR) is activated to relieve the stress on the ER. Current evidence indicates that A. fumigatus relies upon this pathway to sustain the high rate of protease secretion needed to grow optimally in mammalian tissue. In addition, the UPR strengthens the ability of the secretory system to deliver cell wall and membrane components to the hyphal apex, which promotes the invasive growth of the expanding hyphae and protects the fungus from damage caused by antifungal drugs. The important contribution of UPR-dependent functions to the pathogenesis of invasive aspergillosis and antifungal susceptibility suggests that components of this pathway could be promising new targets for antifungal therapy.
烟曲霉建立和维持感染的能力需要持续的营养供应来为能量产生和生长提供燃料。像其他丝状真菌一样，烟曲霉通过吸收来获取营养，这种营养方式依赖于细胞外水解酶的分泌，将宿主组织中的复杂有机聚合物降解为碳和氮的还原形式。如果内质网（ER）的折叠能力在高分泌活性期间超过，则激活称为未折叠蛋白反应（UPR）的信号通路，以减轻 ER 上的压力。目前的证据表明，烟曲霉依赖该途径来维持最佳生长所需的蛋白酶分泌的高速率。此外，UPR 增强了分泌系统向菌丝尖端输送细胞壁和膜成分的能力，这促进了扩展菌丝的侵袭性生长，并保护真菌免受抗真菌药物造成的损害。UPR 依赖性功能对侵袭性曲霉病和抗真菌药物敏感性的重要贡献表明，该途径的成分可能是抗真菌治疗的有前途的新靶点。
