Skn7p Is Involved in Oxidative Stress Response and Virulence of Candida glabrata

Skn7p Is Involved in Oxidative Stress Response and Virulence of Candida glabrata
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DOI:
10.1007/s11046-009-9233-5
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发表时间:
2010-02
期刊:
影响因子:
5.5
通讯作者:
Tomomi Saijo;T. Miyazaki;K. Izumikawa;Tomo Mihara;T. Takazono;K. Kosai;Y. Imamura;M. Seki;H. Kakeya;Yoshihiro Yamamoto;K. Yanagihara;S. Kohno
Tomomi Saijo;T. Miyazaki;K. Izumikawa;Tomo Mihara;T. Takazono;K. Kosai;Y. Imamura;M. Seki;H. Kakeya;Yoshihiro Yamamoto;K. Yanagihara;S. Kohno
中科院分区:
生物学3区
文献类型:
--
作者:
Tomomi Saijo;T. Miyazaki;K. Izumikawa;Tomo Mihara;T. Takazono;K. Kosai;Y. Imamura;M. Seki;H. Kakeya;Yoshihiro Yamamoto;K. Yanagihara;S. Kohno

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光滑念珠菌是一种机会致病真菌,可引起人类浅表和深部真菌病。Skn7p是酵母和几种病原真菌中参与氧化应激反应(oxidative stress response,OSR)的转录因子,但其同源基因在酵母中的功能研究较少。光滑的在这项研究中,我们构建了一个C。glabrataskn7缺失菌株的OSR和毒力相关的突变表型进行了研究。C. glabrataskn 7缺失者对过氧化氢和叔丁基过氧化氢的敏感性增加。我们的实时荧光定量PCR检测结果显示,与野生型对照组相比,过氧化氢处理后,Skn7缺失体中TRX2、TRR1、TSA 1和CTA 1等Skn7p靶基因的转录没有被完全诱导,这与易感表型一致。此外,SKN7的缺失导致在播散性念珠菌病小鼠模型中的毒力减弱。这些结果表明,Skn7p可能在转录调控其靶基因所需的OSR和毒力在C。光滑的
Candida glabratais an opportunistic fungal pathogen that causes both superficial and deep-seated mycosis in humans. InSaccharomyces cerevisiaeand several pathogenic fungi, Skn7p is known as a transcriptional factor involved in oxidative stress response (OSR) but functions of its ortholog have been little investigated inC. glabrata. In this study, we constructed aC. glabrataskn7deletion strain by the ura-blaster technique and investigated mutant phenotypes related to OSR and virulence. TheC. glabrataskn7deletant showed increased susceptibility to hydrogen peroxide andtert-butyl hydroperoxide. Our transcriptional assay evaluated by quantitative real-time PCR revealed that, in response to the treatment with hydrogen peroxide, transcription of some putative Skn7p target genes includingTRX2,TRR1,TSA1andCTA1were not fully induced in theskn7deletant compared to the wild-type control, consistent with the susceptibility phenotype. Furthermore, the deletion ofSKN7resulted in attenuated virulence in a murine model of disseminated candidiasis. These results suggest that Skn7p may play a role in transcriptional regulation of its target genes required for OSR and virulence inC. glabrata.