Functional analysis of the superoxide dismutase family in Aspergillus fumigatus
Functional analysis of the superoxide dismutase family in Aspergillus fumigatus
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DOI：
10.1111/j.1365-2958.2009.07024.x
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发表时间：
2010-02-01
影响因子：
3.6
通讯作者：
Latge, Jean-Paul
中科院分区：
文献类型：
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作者：
Lambou, Karine;Lamarre, Claude;Latge, Jean-Paul
据报道，吞噬细胞产生的反应性氧化剂参与了烟曲霉的杀灭。解毒超氧阴离子的真菌超氧化物歧化酶（SOD）可能是这种机会性病原体的假定毒力因子。在烟曲霉基因组中已鉴定出编码假定的 Sod 的四个基因：细胞质 Cu/ZnSOD (AfSod1p)、线粒体 MnSOD (AfSod2p)、细胞质 MnSOD (AfSod3p) 和显示 MnSOD C 末端结构域的 AfSod4。在生长过程中，AfSOD1和AfSOD2在分生孢子中高表达，而AfSOD3仅在菌丝体中高表达。与其他 SOD 相比，AfSOD4 的表达较弱。 AfSOD4 的缺失是致命的。 Delta sod1 和 Delta sod2 突变体在高温下表现出生长抑制和对甲萘醌过敏，而 sod3 突变体在高温下仅具有轻微的生长延迟。多个突变仅对表型产生累加效应。 sod1/sod2/sod3三重突变体的特征是分生孢子萌发延迟、长时间储存期间分生孢子存活率降低、对甲萘醌的敏感性最高以及对免疫活性小鼠肺泡巨噬细胞杀伤的敏感性增加。尽管存在这些表型，但在免疫受损动物的实验鼠曲霉病模型中，三重突变体和亲本菌株之间没有观察到显着的毒力差异。
P>Reactive oxidant species produced by phagocytes have been reported as being involved in the killing of Aspergillus fumigatus. Fungal superoxide dismutases (SODs) that detoxify superoxide anions could be putative virulence factors for this opportunistic pathogen. Four genes encoding putative Sods have been identified in the A. fumigatus genome: a cytoplasmic Cu/ZnSOD (AfSod1p), a mitochondrial MnSOD (AfSod2p), a cytoplasmic MnSOD (AfSod3p) and AfSod4 displaying a MnSOD C-terminal domain. During growth, AfSOD1 and AfSOD2 were highly expressed in conidia whereas AfSOD3 was only strongly expressed in mycelium. AfSOD4 was weakly expressed compared with other SODs. The deletion of AfSOD4 was lethal. Delta sod1 and Delta sod2 mutants showed a growth inhibition at high temperature and a hypersensitivity to menadione whereas the sod3 mutant had only a slight growth delay at high temperature. Multiple mutations had only an additive effect on the phenotype. The triple sod1/sod2/sod3 mutant was characterized by a delay in conidial germination, a reduced conidial survival during storage overtime, the highest sensitivity to menadione and an increased sensitivity to killing by alveolar macrophage of immunocompetent mice. In spite of these phenotypes, no significant virulence difference was observed between the triple mutant and parental strain in experimental murine aspergillosis models in immunocompromised animals.