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A novel family of dehydrin-like proteins is involved in stress response in the human fungal pathogen Aspergillus fumigatus

机译:新型脱水蛋白样蛋白家族参与了人类真菌病原体烟曲霉的应激反应

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摘要

During a search for genes controlling conidial dormancy in Aspergillus fumigatus, two dehydrin-like genes, DprA and DprB, were identified. The deduced proteins had repeated stretches of 23 amino acids that contained a conserved dehydrin-like protein (DPR) motif. Disrupted DprAΔ mutants were hypersensitive to oxidative stress and to phagocytic killing, whereas DprBΔ mutants were impaired in osmotic and pH stress responses. However, no effect was observed on their pathogenicity in our experimental models of invasive aspergillosis. Molecular dissection of the signaling pathways acting upstream showed that expression of DprA was dependent on the stress-activated kinase SakA and the cyclic AMP-protein kinase A (cAMP-PKA) pathways, which activate the bZIP transcription factor AtfA, while expression of DprB was dependent on the SakA mitogen-activated protein kinase (MAPK) pathway, and the zinc finger transcription factor PacC. Fluorescent protein fusions showed that both proteins were associated with peroxisomes and the cytosol. Accordingly, DprA and DprB were important for peroxisome function. Our findings reveal a novel family of stress-protective proteins in A. fumigatus and, potentially, in filamentous ascomycetes.
机译:在寻找控制烟曲霉中分生孢子休眠的基因的过程中,发现了两个脱水蛋白样基因DprA和DprB。推导的蛋白质具有包含保守的脱水蛋白样蛋白质(DPR)基序的23个氨基酸的重复序列。破坏的DprAΔ突变体对氧化应激和吞噬杀伤反应非常敏感,而DprBΔ突变体的渗透压和pH胁迫反应受损。但是,在我们的侵袭性曲霉病实验模型中,未观察到对其致病性的影响。上游信号通路的分子解剖表明,DprA的表达依赖于应力激活的激酶SakA和环状AMP-蛋白激酶A(cAMP-PKA)通路,后者激活bZIP转录因子AtfA,而DprB的表达则取决于依赖于SakA丝裂原激活的蛋白激酶(MAPK)途径和锌指转录因子PacC。荧光蛋白融合显示这两种蛋白均与过氧化物酶体和胞质溶胶相关。因此,DprA和DprB对于过氧化物酶体功能很重要。我们的发现揭示了在烟曲霉,以及潜在地在丝状子囊藻中的一种新的应激保护蛋白家族。

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