CTA4 transcription factor mediates induction of nitrosative stress response in Candida albicans
CTA4 transcription factor mediates induction of nitrosative stress response in Candida albicans
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DOI：
10.1128/ec.00240-07
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发表时间：
2008-02-01
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影响因子：
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通讯作者：
Gustin, Michael C.
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文献类型：
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作者：
Chiranand, Wiriya;McLeod, Ian;Gustin, Michael C.
这项工作已经确定了主要的真菌病原体白色念珠菌，使亚硝化应激反应的调控元件。一氧化氮（NO）是由宿主免疫系统的巨噬细胞和肠道细菌产生的，抵抗其毒性的能力是促进C.人体内的白色念珠菌暴露C。白念珠菌对NO诱导的黄素血红蛋白Yhb 1 p的上调。这种蛋白质通过酶促将NO转化为无害的硝酸盐来提供保护，但目前尚不清楚C。白色念珠菌能够检测其环境中的NO，因此仅在需要时启动这种防御。我们分析了这个问题，通过逐步突变的YHB 1调节区，以确定一氧化氮敏感性所需的一氧化氮反应元件（NORE）。五个转录因子的候选人的Zn（II）2-Cys 6家庭，然后从粗全细胞提取物中分离，通过使用磁珠涂有这种DNA元素。在这五个基因中，只有CTA 4基因的缺失阻止了亚硝化应激过程中YHB 1转录的诱导，并引起了对NO供体二亚丙基三胺NONOate的生长敏感性; CTA 4p在体内与来自YHB 1调控区的NORE DNA相关联。CTA 4的缺失导致毒力的小但显著的降低。由SSU 1编码的CTA 4依赖性亚硫酸盐转运蛋白也参与NO反应，但C.白色念珠菌ssu 1突变体不敏感，NO，在酿酒酵母的研究结果相反。Cta 4p是第一个被发现在C.白色念珠菌
This work has identified regulatory elements in the major fungal pathogen Candida albicans that enable response to nitrosative stress. Nitric oxide (NO) is generated by macrophages of the host immune system and commensal bacteria, and the ability to resist its toxicity is one adaptation that promotes survival of C. albicans inside the human body. Exposing C. albicans to NO induces upregulation of the flavohemoglobin Yhb1p. This protein confers protection by enzymatically converting NO to harmless nitrate, but it is unknown how C. albicans is able to detect NO in its environment and thus initiate this defense only as needed. We analyzed this problem by incrementally mutating the YHB1 regulatory region to identify a nitric oxide-responsive element (NORE) that is required for NO sensitivity. Five transcription factor candidates of the Zn(II) 2-Cys6 family were then isolated from crude whole-cell extracts by using magnetic beads coated with this DNA element. Of the five, only deletion of the CTA4 gene prevented induction of YHB1 transcription during nitrosative stress and caused growth sensitivity to the NO donor dipropylenetriamine NONOate; Cta4p associates in vivo with NORE DNA from the YHB1 regulatory region. Deletion of CTA4 caused a small but significant decrease in virulence. A CTA4-dependent putative sulfite transporter encoded by SSU1 is also implicated in NO response, but C. albicans ssu1 mutants were not sensitive to NO, in contrast to findings in Saccharomyces cerevisiae. Cta4p is the first protein found to be necessary for initiating NO response in C. albicans.