A novel role of the ferric reductase Cfl1 in cell wall integrity, mitochondrial function, and invasion to host cells in Candida albicans.
A novel role of the ferric reductase Cfl1 in cell wall integrity, mitochondrial function, and invasion to host cells in Candida albicans.
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DOI：
10.1111/1567-1364.12194
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发表时间：
2014-11
影响因子：
3.2
通讯作者：
Qilin Yu;Yijie Dong;Ning Xu;Kefan Qian;Yulu Chen;Biao Zhang;L. Xing;Mingchun Li
中科院分区：
文献类型：
--
作者：
Qilin Yu;Yijie Dong;Ning Xu;Kefan Qian;Yulu Chen;Biao Zhang;L. Xing;Mingchun Li
白色念珠菌是一种重要的机会性致病菌，可引起浅表黏膜感染和危及生命的全身疾病。铁的获取是病原菌-宿主相互作用的重要因素，也是该菌致病性的重要因素。铁还原酶将铁转化为亚铁，是高亲和力铁摄取系统的重要组成部分。序列分析已经在白念珠菌基因组中鉴定出至少17个可能的铁还原酶基因。CFL1是第一个在白色念珠菌中发现的铁还原酶。然而，对其在白念珠菌生理学和致病性中的作用知之甚少。在本研究中，我们发现CFL1的突变导致了对化学和物理细胞壁胁迫的高度敏感，细胞壁完整性(CWI)途径的激活，细胞壁组成的异常，以及分泌增加，表明该突变体的CWI存在缺陷。此外，该突变体表现出异常的线粒体活性和形态，表明铁还原酶与线粒体功能有关。此外，该突变体对聚苯乙烯微板和口腔上皮细胞的黏附能力降低，对宿主上皮细胞的侵袭能力降低。这些发现揭示了白色念珠菌Cfl1在维持CWI、线粒体功能以及该病原体与宿主之间的相互作用中的新作用。
Candida albicans is an important opportunistic pathogen, causing both superficial mucosal infections and life-threatening systemic diseases. Iron acquisition is an important factor for pathogen-host interaction and also a significant element for the pathogenicity of this organism. Ferric reductases, which convert ferric iron into ferrous iron, are important components of the high-affinity iron uptake system. Sequence analyses have identified at least 17 putative ferric reductase genes in C. albicans genome. CFL1 was the first ferric reductase identified in C. albicans. However, little is known about its roles in C. albicans physiology and pathogenicity. In this study, we found that disruption of CFL1 led to hypersensitivity to chemical and physical cell wall stresses, activation of the cell wall integrity (CWI) pathway, abnormal cell wall composition, and enhanced secretion, indicating a defect in CWI in this mutant. Moreover, this mutant showed abnormal mitochondrial activity and morphology, suggesting a link between ferric reductases and mitochondrial function. In addition, this mutant displayed decreased ability of adhesion to both the polystyrene microplates and buccal epithelial cells and invasion of host epithelial cells. These findings revealed a novel role of C. albicans Cfl1 in maintenance of CWI, mitochondrial function, and interaction between this pathogen and the host.