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Ecm7 是 HACS 的调节剂,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。

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

机构信息

Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Science, Nankai University, Tianjin, PR China.

出版信息

Fungal Genet Biol. 2013 Aug;57:23-32. doi: 10.1016/j.fgb.2013.05.010. Epub 2013 Jun 13.

Abstract

Calcium is a universal messenger that translates diverse environmental stresses and developmental cues into specific cellular and developmental responses. In yeast, Cch1 and Mid1 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 ecm7Δ/Δ cells were hypersensitive to oxidative stress. ECM7 deletion induced the degradation of Cap1 when exposed to H₂O₂ treatment. Besides, the ecm7Δ/Δ 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 ecm7Δ/Δ 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.

摘要

钙是一种普遍的信使,它将不同的环境压力和发育线索转化为特定的细胞和发育反应。在酵母中,Cch1 和 Mid1 作为高亲和力 Ca²⁺内流系统(HACS)的一部分发挥作用,该系统在受到突然刺激时迅速激活。在这里,我们报告说,HACS 的调节剂 Ecm7 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重要作用。ECM7 的破坏导致对钙缺乏条件的敏感性增加。流式细胞术分析显示,Ecm7 在高 pH 冲击下介导 Ca²⁺内流。环己酰亚胺追踪实验进一步表明,MID1 缺失显著降低了 Ecm7 的稳定性。我们还提供了证据表明,ecm7Δ/Δ 细胞对氧化应激更敏感。ECM7 缺失诱导 Cap1 在暴露于 H₂O₂处理时降解。此外,ecm7Δ/Δ 突变体在菌丝发育方面存在缺陷,伴随着菌丝相关基因 HWP1 的表达降低。尽管随后的实验表明,ecm7Δ/Δ 突变体与野生型菌株具有相似的毒力,但突变体在小鼠肾脏中的侵袭和扩散能力下降。总之,Ecm7 在白色念珠菌的适应和致病性中发挥重要作用。

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