Ecm7, a regulator of HACS, functions in calcium homeostasis maintenance, oxidative stress response and hyphal development in Candida albicans

Ecm7, a regulator of HACS, functions in calcium homeostasis maintenance, oxidative stress response and hyphal development in Candida albicans
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Ecm7 是 HACS 的调节因子,在白色念珠菌的钙稳态维持、氧化应激反应和菌丝发育中发挥作用

DOI:
10.1016/j.fgb.2013.05.010
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发表时间:
2013-08-01
影响因子:
3
通讯作者:
Li, Mingchun
Li, Mingchun
中科院分区:
生物学3区
文献类型:
--
作者:
Ding, Xiaohui;Yu, Qilin;Li, Mingchun

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钙是一种通用的信使,可以将不同的环境压力和发育信号转化为特定的细胞和发育反应。在酵母中,Cch1和Midi作为高亲和力钙内流系统(HACS)的一部分发挥作用,该系统对突然的刺激反应迅速激活。在此,我们报道了HACS的调节因子Ecm7在维持白色念珠菌的钙稳态、氧化应激反应和菌丝发育过程中发挥着重要作用。ECM7的中断导致对缺钙条件的敏感性增加。流式细胞仪分析表明,在高pH休克条件下,ECM7介导了细胞内钙内流。放线菌亚胺追逐实验进一步表明,MID1缺失显著降低了ECM7的稳定性。我们还提供了ecm7 Delta/Delta细胞对氧化应激敏感的证据。在H_2O_2作用下,ECM7缺失可诱导Cap1降解。此外,ecm7 Delta/Delta突变体菌丝发育存在缺陷,并伴有菌丝相关基因HWP1表达下降。虽然随后的实验表明ecm7 Delta/Delta突变株表现出与野生型毒力相似的毒力,但该突变株在小鼠肾脏的侵袭和扩散能力下降。综上所述,ECM7在白念珠菌的适应和致病过程中发挥着重要作用。(C)2013 Elsevier Inc.保留所有权利。
Calcium is a universal messenger that translates diverse environmental stresses and developmental cues into specific cellular and developmental responses. In yeast, Cch1 and Midi function as part of a high affinity Ca2+ influx system (HACS) that becomes activated rapidly in response to sudden stimuli. Here, we report that Ecm7, a regulator of HACS, plays important roles in calcium homeostasis maintenance, oxidative stress response and hyphal development in Candida albicans. Disruption of ECM7 led to increased sensitivity to calcium-depleted conditions. Flow cytometry analysis revealed that Ecm7 mediated Ca2+ influx under high pH shock. Cycloheximide chase experiments further showed that MID1 deletion significantly decreased the stability of Ecm7. We also provided evidences that ecm7 Delta/Delta cells were hypersensitive to oxidative stress. ECM7 deletion induced the degradation of Cap1 when exposed to H2O2 treatment. Besides, the ecm7 Delta/Delta mutant showed a defect in hyphal development, which was accompanied with the decreased expression of hyphal related gene HWP1. Though subsequent experiments revealed that the ecm7 Delta/Delta mutant showed similar virulence to the wild-type strain, the ability of invasion and diffusion of the mutant in mouse kidneys decreased. Taken together, Ecm7 plays important roles in the adaptation and pathogenicity of C albicans. (C) 2013 Elsevier Inc. All rights reserved.