Identification of a novel response regulator, Crr1, that is required for hydrogen peroxide resistance in Candida albicans.
Identification of a novel response regulator, Crr1, that is required for hydrogen peroxide resistance in Candida albicans.
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DOI：
10.1371/journal.pone.0027979
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Quinn J
中科院分区：
文献类型：
--
作者：
Bruce CR;Smith DA;Rodgers D;da Silva Dantas A;MacCallum DM;Morgan BA;Quinn J
白色念珠菌在人类体内定植许多生态位，因此其作为病原体的成功取决于其适应宿主体内不同生长环境的能力。双组分信号转导是细菌响应环境刺激的常见机制，虽然不太常见，但在真菌中也具有双组分相关途径的特征。在这里，我们报告了白色念珠菌中一种新型双组分反应调节蛋白的鉴定和表征，我们将其命名为 CRR1（念珠菌反应调节蛋白 1）。 Crr1 包含响应调节蛋白特征的接收器结构域，包括从上游组氨酸激酶接收磷酸盐的保守天冬氨酸。值得注意的是，CRR1 的直系同源物仅存在于属于念珠菌 CTG 分支的真菌中。白色念珠菌 CRR1 基因的缺失，或预测的磷酸天冬氨酸的突变，会导致细胞对氧化剂过氧化氢的敏感性增加。 Crr1 存在于细胞质和细胞核中，并且这种定位不受氧化应激或预测的磷酸天冬氨酸突变的影响。此外，与 Ssk1 反应调节因子不同，Crr1 不是过氧化氢诱导的 Hog1 应激激活蛋白激酶途径激活所必需的，也不是全身性疾病小鼠模型中白色念珠菌的毒力所必需的。综上所述，我们的数据表明，Crr1 是一种仅限于念珠菌 CTG 进化枝的新型反应调节因子，它以不依赖于 Hog1 的方式调节白色念珠菌细胞对过氧化氢的反应，而这种方式需要保守的磷酸天冬氨酸的功能。
Candida albicans colonises numerous niches within humans and thus its success as a pathogen is dependent on its ability to adapt to diverse growth environments within the host. Two component signal transduction is a common mechanism by which bacteria respond to environmental stimuli and, although less common, two component-related pathways have also been characterised in fungi. Here we report the identification and characterisation of a novel two component response regulator protein in C. albicans which we have named CRR1 (Candida Response Regulator 1). Crr1 contains a receiver domain characteristic of response regulator proteins, including the conserved aspartate that receives phosphate from an upstream histidine kinase. Significantly, orthologues of CRR1 are present only in fungi belonging to the Candida CTG clade. Deletion of the C. albicans CRR1 gene, or mutation of the predicted phospho-aspartate, causes increased sensitivity of cells to the oxidising agent hydrogen peroxide. Crr1 is present in both the cytoplasm and nucleus, and this localisation is unaffected by oxidative stress or mutation of the predicted phospho-aspartate. Furthermore, unlike the Ssk1 response regulator, Crr1 is not required for the hydrogen peroxide-induced activation of the Hog1 stress-activated protein kinase pathway, or for the virulence of C. albicans in a mouse model of systemic disease. Taken together, our data suggest that Crr1, a novel response regulator restricted to the Candida CTG clade, regulates the response of C. albicans cells to hydrogen peroxide in a Hog1-independent manner that requires the function of the conserved phospho-aspartate.
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影响因子：
5.4
作者：
Brown, Alistair J. P.;Haynes, Ken;Quinn, Janet
通讯作者：
Quinn, Janet
影响因子：
--
作者：
Chauhan, N;Inglis, D;Calderone, R
通讯作者：
Calderone, R
影响因子：
3
作者：
Dennison, PMJ;Ramsdale, M;Brown, AJP
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影响因子：
3.1
作者：
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通讯作者：
Calderone, R
影响因子：
5.6
作者：
KLOSE, KE;WEISS, DS;KUSTU, S
通讯作者：
KUSTU, S