title: A novel role of the ferric reductase Cfl1 in cell wall integrity, mitochondrial function, and invasion to host cells in Candida albicans.
abstract: 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.
authors.affiliation: Department of Microbiology, Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin, China.
authors.forename: Qilin
authors.initials: Q
authors.lastname: Yu
authors.forename: Yijie
authors.initials: Y
authors.lastname: Dong
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
authors.forename: Kefan
authors.initials: K
authors.lastname: Qian
authors.forename: Yulu
authors.initials: Y
authors.lastname: Chen
authors.forename: Biao
authors.initials: B
authors.lastname: Zhang
authors.forename: Laijun
authors.initials: L
authors.lastname: Xing
authors.forename: Mingchun
authors.initials: M
authors.lastname: Li
mesh_terms: D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D002448:Cell Adhesion; D002473:Cell Wall / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D004705:Endocytosis; D004847:Epithelial Cells / Q000382:microbiology; D038181:FMN Reductase / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D054884:Host-Pathogen Interactions; D006801:Humans; D008853:Microscopy; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D037521:Virulence Factors; D010088:Oxidoreductases; C102678:CFL1 protein, Candida albicans; D038181:FMN Reductase; C023903:ferric citrate iron reductase
keywords: Candida albicans; adhesion; cell wall integrity; ferric reductase; invasion