Transcriptional profiling of the Candida albicans Ssk1p receiver domain point mutants and their virulence.
Transcriptional profiling of the Candida albicans Ssk1p receiver domain point mutants and their virulence.
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DOI：
10.1111/j.1567-1364.2008.00404.x
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发表时间：
2008-08
影响因子：
3.2
通讯作者：
Chauhan N
中科院分区：
文献类型：
--
作者：
Menon V;De Bernardis F;Calderone R;Chauhan N
白色念珠菌的Ssk 1 p反应调节因子是氧化适应、人中性粒细胞存活和播散性小鼠念珠菌病模型毒力所必需的。Ssk 1 p的活性通过HOG 1 MAP激酶途径（HOG=高渗甘油）发出信号。此外，我们以前已经表明，氨基酸残基D556和D513的Ssk 1 p接收域的Ssk 1 p的氧化应激适应和形态发生的活动是至关重要的。在此，我们使用转录谱来解释氧化剂的敏感性和缺陷的形态发生的两个点突变体（D556 N和D513 K，分别）相比，野生型菌株。在氧化应激期间，与WT细胞相比，D556 N突变体中（5 mM H2 O2）时，与氧化还原稳态和氧化应激相关的基因发生下调，占所有基因变化的约5%，包括SOD 1（超氧化物歧化酶），CAP 1（某些形式的氧化剂适应所需的转录因子）和三个编码谷胱甘肽生物合成蛋白（GLR 1、GSH 1和GSH 2）的基因。突变体SSK 26（D513 K）对过氧化物不敏感，但在其酵母到菌丝的转变中受损。我们注意到与形态发生和细胞伸长相关的基因下调。还在念珠菌病的大鼠阴道炎模型中评价了每个突变体的毒力。SSK 1无效突变体（菌株SSK 2 -1）和SSK 25从阴道腔中的清除率显著高于野生型（CAF 2 -1）或D513 K突变体（D513 K），表明Ssk 1 p的单个氨基酸的特定变化可能会改变该菌株在大鼠阴道粘膜中定殖的能力。
The Ssk1p response regulator of Candida albicans is required for oxidant adaptation, survival in human neutrophils, and virulence in a disseminated murine model of candidiasis. The activities of the Ssk1p are signaled through the HOG1 MAP kinase pathway (HOG=hyperosmotic glycerol). Further, we have previously shown that the amino acid residues D556 and D513 of the Ssk1p receiver domain are critical to the activities of the Ssk1p in oxidant stress adaptation and morphogenesis. Herein, we use transcriptional profiling to explain the oxidant sensitivity and defect in morphogenesis of two point mutants (D556N and D513K, respectively) compared to a WT strain. In the D556N mutant compared to WT cells during oxidative stress (5mM H2O2), a down regulation of genes associated with redox homeostasis and oxidative stress occurred that accounted for about 5% of all gene changes, including among others, SOD1 (superoxide dismutase), CAP1 (transcription factor required for some forms of oxidant adaptation), and three genes encoding glutathione biosynthesis proteins (GLR1, GSH1, and GSH2). Mutant SSK26 (D513K) was not sensitive to peroxide but was impaired in its yeast to hyphal transition. We noted down regulation of genes associated with morphogenesis and cell elongation. Virulence of each mutant was also evaluated in a rat vaginitis model of candidiasis. Clearance of the SSK1 null mutant (strain SSK21) and SSK25 from the vaginal canal was significantly greater than wild type (CAF2-1) or the D513K mutant (D513K), indicating that a specific change in a single amino acid of the Ssk1p may alter the ability of this strain to colonize the rat vaginal mucosa.
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影响因子：
2.8
作者：
Arana, DM;Nombela, C;Pla, J
通讯作者：
Pla, J
影响因子：
--
作者：
Chauhan, N;Inglis, D;Calderone, R
通讯作者：
Calderone, R
影响因子：
3.1
作者：
Calera, JA;Zhao, XJ;Calderone, R
通讯作者：
Calderone, R
影响因子：
11.4
作者：
Posas, F;Saito, H
通讯作者：
Saito, H
影响因子：
64.8
作者：
MAEDA, T;WURGLERMURPHY, SM;SAITO, H
通讯作者：
SAITO, H