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Morphological transition and iron metabolism are closely relevant to  Candida albicans  pathogenicity and virulence. In our previous study, we demonstrated that  C. albicans  Aft2 plays an important role in ferric reductase activity and virulence. Here, we further explored the roles of  C. albicans  Aft2 in numerous cellular processes. We found that  C. albicans  Aft2 exhibited an important role in iron metabolism through bi-directional regulation effects on iron-regulon expression. Deletion of  AFT2  reduced cellular iron accumulation under iron-deficient conditions. Furthermore, both reactive oxygen species (ROS) generation and superoxide dismutase (SOD) activity were remarkably increased in the  aft2Δ/Δ  mutant, which were thought to be responsible for the defective responses to oxidative stress. However, we found that over-expression of  C. albicans AFT2  under the regulation of the strong  PGK1  promoter could not effectively rescue  Saccharomyces cerevisiae aft1Δ  mutant defects in some cellular processes, such as cell-wall assembly, ion homeostasis and alkaline resistance, suggesting a possibility that  C. albicans  Aft2 weakened its functional role of regulating some cellular metabolism during the evolutionary process. Interestingly, deletion of  AFT2  in  C. albicans  increased cell surface hydrophobicity, cell flocculation and the ability of adhesion to polystyrene surfaces. In addition, our results also revealed that  C. albicans  Aft2 played a dual role in regulating hypha-specific genes under solid and liquid hyphal inducing conditions. Deletion of  AFT2  caused an impaired invasive growth in solid medium, but an increased filamentous aggregation and growth in liquid conditions. Moreover, iron deficiency and environmental cues induced nuclear import of Aft2, providing additional evidence for the roles of Aft2 in transcriptional regulation.

Aft2, a Novel Transcription Regulator, Is Required for Iron Metabolism, Oxidative Stress, Surface Adhesion and Hyphal Development in Candida albicans