Two glutathione peroxidases in the fungal pathogen Cryptococcus neoformans are expressed in the presence of specific substrates
Two glutathione peroxidases in the fungal pathogen Cryptococcus neoformans are expressed in the presence of specific substrates
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DOI：
10.1099/mic.0.28132-0
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发表时间：
2005-08-01
期刊：
影响因子：
2.8
通讯作者：
Lodge, JK
中科院分区：
文献类型：
--
作者：
Missall, TA;Cherry-Harris, JF;Lodge, JK
谷胱甘肽过氧化物酶催化还原型谷胱甘肽还原过氧化物酶。为了确定这些酶是否在抵抗氧化应激和新生隐球菌逃避天然免疫系统方面起重要作用，我们鉴定并研究了两个具有38%同源性的谷胱甘肽过氧化物酶同源物。在这项研究中，这些过氧化物酶，GPX1和Gpx2，它们的定位，它们对总谷胱甘肽过氧化物酶活性的贡献，以及它们在新生隐孢子菌的氧化和亚硝化胁迫抗性中的重要性。结果表明，这两个谷胱甘肽过氧化物酶基因在胁迫反应中存在差异表达。而GPX1和GPX2在叔丁基氢过氧化氢或异丙苯氢过氧化氢胁迫下均被诱导，而在一氧化氮应激中被抑制，而只有GPX2在过氧化氢胁迫下被诱导。产生了谷胱甘肽过氧化物酶的缺失突变体，发现它们对各种过氧化胁迫敏感，但对其他氧化剂胁迫(如超氧化物和一氧化氮)表现出野生型抗性。虽然谷胱甘肽过氧化物酶突变体对巨噬细胞的氧化剂杀伤略有敏感，但它们在隐球菌病的小鼠模型中表现出野生型毒力。
Glutathione peroxidases catalyse the reduction of peroxides by reduced glutathione. To determine if these enzymes are important for resistance to oxidative stress and evasion of the innate immune system by the fungal pathogen Cryptococcus neoformans, two glutathione peroxidase homologues, which share 38% identity, were identified and investigated. In this study, these peroxidases, Gpx1 and Gpx2, their localization, their contribution to total glutathione peroxidase activity, and their importance to the oxidative and nitrosative stress resistance of C. neoformans are described. It is shown that the two glutathione peroxidase genes are differentially expressed in response to stress. While both GPX1 and GPX2 are induced during t-butylhydroperoxide or cumene hydroperoxide stress and repressed during nitric oxide stress, only GPX2 is induced in response to hydrogen peroxide stress. Deletion mutants of each and both of the glutathione peroxidases were generated, and it was found that they are sensitive to various peroxide stresses while showing wild-type resistance to other oxidant stresses, such as superoxide and nitric oxide. While the glutathione peroxidase mutants are slightly sensitive to oxidant killing by macrophages, they exhibit wild-type virulence in a mouse model of cryptococcosis.