The copper regulon of the human fungal pathogen Cryptococcus neoformans H99.
The copper regulon of the human fungal pathogen Cryptococcus neoformans H99.
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DOI：
10.1111/j.1365-2958.2011.07794.x
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发表时间：
2011-09
影响因子：
3.6
通讯作者：
Thiele DJ
中科院分区：
文献类型：
--
作者：
Ding C;Yin J;Tovar EM;Fitzpatrick DA;Higgins DG;Thiele DJ
新型隐球菌是一种人类真菌病原体，在免疫功能低下的宿主中是隐球菌病和致命脑膜炎的病原体。最近的研究表明，铜（Cu）获取在新生C.的毒力中起着重要作用，因为在小鼠模型中缺乏Cuf1的突变体是低毒力的。Cuf1可以激活Ctr4高亲和力的铜进口蛋白。为了了解C.新生生物中铜反应基因群及其表达对毒力的影响，我们确定了C.新生生物在Cu升高或Cu缺乏时的转录谱。我们发现了两个金属硫蛋白基因（CMT1和CMT2），编码富含半胱氨酸的铜结合和解毒蛋白，它们的表达在过量铜的情况下显著升高。我们发现了一个新的铜转运体CnCtr1，它是由铜缺乏诱导的，与CnCtr4不同，与其他真菌的Ctr1有显著的系统发育关系。令人惊讶的是，与其他真菌相比，我们发现CnCTR1和CnCTR4在Cu限制下的表达诱导，以及CMT1和CMT2对Cu过量的响应，都依赖于cncu1铜金属调节转录因子。这些研究为评估C.新生生物毒力所需的特定Cuf1靶基因奠定了基础。
Cryptococcus neoformans is a human fungal pathogen that is the causative agent of cryptococcosis and fatal meningitis in immuno-compromised hosts. Recent studies suggest that copper (Cu) acquisition plays an important role in C. neoformans virulence, as mutants that lack Cuf1, which activates the Ctr4 high affinity Cu importer, are hypo-virulent in mouse models. To understand the constellation of Cu-responsive genes in C. neoformans and how their expression might contribute to virulence, we determined the transcript profile of C. neoformans in response to elevated Cu or Cu deficiency. We identified two metallothionein genes (CMT1 and CMT2), encoding cysteine-rich Cu binding and detoxifying proteins, whose expression is dramatically elevated in response to excess Cu. We identified a new C. neoformans Cu transporter, CnCtr1, that is induced by Cu deficiency and is distinct from CnCtr4 and which shows significant phylogenetic relationship to Ctr1 from other fungi. Surprisingly, in contrast to other fungal, we found that induction of CnCTR1 and CnCTR4 expression under Cu limitation, and CMT1 and CMT2 in response to Cu excess, are dependent on the CnCuf1 Cu metalloregulatory transcription factor. These studies set the stage for the evaluation of the specific Cuf1 target genes required for virulence in C. neoformans.
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影响因子：
2.8
作者：
Beaudoin, Jude;Thiele, Dennis J.;Puig, Sergi
通讯作者：
Puig, Sergi
影响因子：
11.4
作者：
Egli, D;Selvaraj, A;Schaffner, W
通讯作者：
Schaffner, W
影响因子：
--
作者：
DROMER, F;AUCOUTURIER, P;YENI, P
通讯作者：
YENI, P
DOI：
10.1073/pnas.81.11.3332
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BUTT, TR;STERNBERG, EJ;CROOKE, ST
通讯作者：
CROOKE, ST
影响因子：
2.1
作者：
Divon, Hege H.;Fluhr, Robert
通讯作者：
Fluhr, Robert