College of Life Science, Nankai Universitdy, Tianjin 300071, China.
Mycopathologia. 2012 Dec;174(5-6):359-69. doi: 10.1007/s11046-012-9569-0. Epub 2012 Aug 12.
Ca(2+) channel Cch1, and its subunit Mid1, has been suggested as the protein complex responsible for mediating Ca(2+) influx, which is often employed by fungal cells to maintain cell survival. The abilities of morphological switch and response to stress conditions are closely related to pathogenicity in Candida albicans. Cch1 and Mid1 activity are required for virulence of Cryptococcus neoformans and Claviceps purpurea, respectively. To investigate whether Cch1 and Mid1 also play a role in the virulence of C. albicans, we constructed cch1Δ/Δ and mid1Δ/Δ mutant strains for functional analysis of CCH1 and MID1. Although both of the mutants displayed the ability of yeast-to-hypha transition, they were defective in hyphae maintenance and invasive growth. Interestingly, deletion of CCH1 or MID1 in C. albicans led to an obvious defect phenotype in oxidative stress response. Moreover, the virulence of the mutants was reduced in a mouse model. Our results demonstrated that Cch1 and Mid1 activity are related to the virulence of C. albicans and may provide a new antifungal target.
钙通道 Cch1 及其亚基 Mid1 被认为是介导钙内流的蛋白复合物,真菌细胞常利用钙内流来维持细胞存活。形态转换和应激响应的能力与白色念珠菌的致病性密切相关。Cch1 和 Mid1 的活性分别是新型隐球菌和麦角菌毒力所必需的。为了研究 Cch1 和 Mid1 是否也参与了白色念珠菌的毒力,我们构建了 cch1Δ/Δ 和 mid1Δ/Δ 突变株,以对 CCH1 和 MID1 进行功能分析。尽管这两种突变体都显示出了从酵母到菌丝的转变能力,但它们在菌丝维持和侵袭性生长方面存在缺陷。有趣的是,在白色念珠菌中敲除 CCH1 或 MID1 导致其在氧化应激反应中出现明显缺陷表型。此外,突变体的毒力在小鼠模型中降低。我们的研究结果表明,Cch1 和 Mid1 的活性与白色念珠菌的毒力有关,这可能为抗真菌治疗提供了新的靶点。