Role of Candida albicans Aft2p transcription factor in ferric reductase activity, morphogenesis and virulence.

The ability of Candida albicans to act as an opportunistic fungal pathogen is linked to its ability to switch among different morphological forms. This conversion is an important feature of C. albicans and is correlated with its pathogenesis. Many conserved positive and negative transcription factors regulate morphogenetic transition of C. albicans. Here, we show the results of functional analysis of CaAFT2, which is an orthologue of the Saccharomyces cerevisiae AFT2 gene. We have cloned CaAFT2 which has an ability to complement the S. cerevisiae aft1Δ mutant strain growth defect. Interestingly, although disruption of the AFT2 gene did not affect cell growth in solid and liquid iron-limited conditions, the cell surface ferric reductase activity was significantly decreased. Importantly, deletion of AFT2 in C. albicans led to growth of a smooth colony with no peripheral hyphae. Moreover, virulence of an aft2Δ/aft2Δ mutant was markedly attenuated in a mouse model. Our results suggest that CaAft2p represents a novel activator and that it functions in ferric reductase activity, morphogenesis and virulence in C. albicans.