Grf10 regulates the response to copper, iron, and phosphate in Candida albicans.
Grf10 regulates the response to copper, iron, and phosphate in Candida albicans.
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DOI：
10.1093/g3journal/jkad070
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发表时间：
2023-06-01
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影响因子：
--
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致病酵母、白色念珠菌和其他微生物必须能够应对人体内营养供应的急剧变化。铜、铁和磷是微生物必需的微量营养素，它们被人体宿主隔离为营养免疫；然而，巨噬细胞利用高水平的铜来诱导有毒的氧化应激。Grf10是一种重要的转录因子，参与调控与形态发生(丝状化、厚壁孢子形成)和代谢(腺苷生物合成、1-碳代谢)相关的基因。Δ突变体以基因剂量依赖的方式表现出对过量铜的抗性，但对其他金属(钙、钴、铁、锰和锌)的反应与野生型相同。在蛋白质相互作用区域内的保守残基D302和E305的点突变赋予了对高铜的抗性，并诱导了类似于零等位基因菌株的菌丝形成。GRF10Δ突变体与YPD培养基铜、铁和磷的吸收有关，并对高铜产生正常的转录反应。该突变体积累了较低水平的镁和磷，表明铜的抗性与磷酸盐代谢有关。我们的结果强调了Grf10在白念珠菌铜和磷稳态中的新作用，并强调了Grf10在将这些与细胞生存联系起来的基础作用。
The pathogenic yeast, Candida albicans, and other microbes must be able to handle drastic changes in nutrient availability within the human host. Copper, iron, and phosphate are essential micronutrients for microbes that are sequestered by the human host as nutritional immunity; yet high copper levels are employed by macrophages to induce toxic oxidative stress. Grf10 is a transcription factor important for regulating genes involved in morphogenesis (filamentation, chlamydospore formation) and metabolism (adenylate biosynthesis, 1-carbon metabolism). The grf10Δ mutant exhibited resistance to excess copper in a gene dosage-dependent manner but grew the same as the wild type in response to other metals (calcium, cobalt, iron, manganese, and zinc). Point mutations in the conserved residues D302 and E305, within a protein interaction region, conferred resistance to high copper and induced hyphal formation similar to strains with the null allele. The grf10Δ mutant misregulated genes involved with copper, iron, and phosphate uptake in YPD medium and mounted a normal transcriptional response to high copper. The mutant accumulated lower levels of magnesium and phosphorus, suggesting that copper resistance is linked to phosphate metabolism. Our results highlight new roles for Grf10 in copper and phosphate homeostasis in C. albicans and underscore the fundamental role of Grf10 in connecting these with cell survival.
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影响因子：
15.9
作者：
Brown, Alistair J. P.;Brown, Gordon D.;Netea, Mihai G.;Gow, Neil A. R.
通讯作者：
Gow, Neil A. R.
影响因子：
11.3
作者：
Gerwien F;Skrahina V;Kasper L;Hube B;Brunke S
通讯作者：
Brunke S
影响因子：
3.1
作者：
Correia, Alexandra;Lermann, Ulrich;Pais, Celia
通讯作者：
Pais, Celia
影响因子：
3.1
作者：
Donovan, M;Schumuke, JJ;Dotson, SB
通讯作者：
Dotson, SB
感染过程中铜的阴阳和阳。
DOI：
10.1007/s00775-016-1335-1
发表时间：
2016-04
期刊：
Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry
影响因子：
--
作者：
Besold AN;Culbertson EM;Culotta VC
通讯作者：
Culotta VC