In vivo transcript profiling of Candida albicans identifies a gene essential for interepithelial dissemination
In vivo transcript profiling of Candida albicans identifies a gene essential for interepithelial dissemination
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DOI：
10.1111/j.1462-5822.2007.01009.x
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发表时间：
2007-12-01
影响因子：
3.4
通讯作者：
Hube, Bernhard
中科院分区：
文献类型：
--
作者：
Zakikhany, Katherina;Naglik, Julian R.;Hube, Bernhard
白色念珠菌是人类最常见的口腔真菌病原体，但其致病机制尚不清楚。白色念珠菌是否侵入并持续存在于粘膜上皮尚不清楚。为了了解口腔发病机制，我们使用重建的人口腔上皮（RHE）表征上皮-真菌相互作用的细胞和分子机制。我们观察到菌丝的形成通过主动（物理渗透）和被动（诱导内吞）过程促进上皮细胞的侵袭。C.全基因组转录谱分析将白色念珠菌实验性RHE感染与11例假膜性念珠菌病患者样本进行比较，以鉴定与体内疾病发展相关的基因。表达谱反映了形态开关和适应性反应，中性pH值，非葡萄糖碳源和亚硝化应激。我们发现了几个新的感染相关基因的未知功能。在RHE感染和患者中上调的一个基因，命名为EED 1，是维持菌丝伸长所必需的。缺乏EED 1的突变体在上皮组织上表现出短暂的细胞伸长，这使得上皮细胞仅能浅表侵入。一旦进入上皮细胞，Delta eed 1细胞可以像酵母或假菌丝一样增殖，但仍被困在细胞内。我们的研究结果表明，适应性反应和形态的C。白色念珠菌在粘膜感染期间对宿主-真菌相互作用起特定作用。
Candida albicans is the most common oral fungal pathogen of humans, but the mechanisms by which C. albicans invades and persists within mucosal epithelium are not clear. To understand oral pathogenesis, we characterized the cellular and molecular mechanisms of epithelial-fungus interactions using reconstituted human oral epithelium (RHE). We observed that hyphal formation facilitates epithelial invasion via both active (physical penetration) and passive (induced endocytosis) processes. Genome wide transcript profiling of C. albicans experimental RHE infection was compared with that from 11 patient samples with pseudomembranous candidiasis to identify genes associated with disease development in vivo. Expression profiles reflected the morphological switch and an adaptive response to neutral pH, non-glucose carbon sources and nitrosative stress. We identified several novel infection-associated genes with unknown function. One gene, upregulated in both RHE infection and patients, named EED1, was essential for maintenance of hyphal elongation. Mutants lacking EED1 showed transient cell elongation on epithelial tissue, which enabled only superficial invasion of epithelial cells. Once inside an epithelial cell, Delta eed1 cells could proliferate as yeasts or pseudohyphae but remained trapped intracellularly. Our results suggest that the adaptive response and morphology of C. albicans play specific roles for host-fungal interactions during mucosal infections.