Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Science, Nankai University, Tianjin, PR China.
Fungal Genet Biol. 2013 Aug;57:23-32. doi: 10.1016/j.fgb.2013.05.010. Epub 2013 Jun 13.
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.
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。
