Many transcriptional regulators play roles in morphogenesis of the human pathogen Candida albicans. Recently, Sfl2, a sequence homolog of C. albicans Sfl1, has been shown to be required for hyphal development. In this report, we show that, like Sfl1, Sfl2 could complement the phenotypes of the Saccharomyces cerevisiae sfl1 mutant, and green fluorescent protein-tagged Sfl2 localized in the nuclei of both yeast and hyphal cells in C. albicans, reflecting its role as a transcriptional regulator. In C. albicans, SFL2 expression was induced at a high growth temperature (37 °C) at both transcriptional and translational levels. The deletion of SFL2 impaired filamentation at a high temperature, whereas the overexpression of SFL2 promoted filamentous growth at a low temperature. Sfl2-activated hyphal development needs the existence of Efg1 and Flo8 under aerobic conditions. Thus, in contrast to Sfl1, which represses filamentation, Sfl2 acts as an activator of filamentous growth in C. albicans. Functional analysis of chimeric Sfl proteins demonstrated that the opposite actions of C. albicans Sfl1 and Sfl2 were mainly mediated by their heat shock factor domains. Furthermore, the deletion of SFL2 attenuated virulence in a mouse model of gastrointestinal colonization and dissemination, indicating that Sfl2 is important for virulence in the gastrointestinal model of candidiasis. Our results provide new insights into Sfl2 functions in C. albicans morphogenesis and pathogenesis.
Edited by Judit OvádiKeywords: Zcf37 Regulator White-opaque switching Candida albicans a b s t r a c t Candida albicans, the most prevalent human fungal pathogen, can switch stochastically between white and opaque phases. In this study, we identified Zcf37, a zinc finger protein, as a new regulator of white-opaque switching. Deletion of ZCF37 increased white-to-opaque switching frequency and stabilized the opaque state. Overexpression of ZCF37 promoted conversion of opaque cells to white phase, but needed existence of Efg1, a key regulator required for maintenance of the white state. Deletion of EFG1 abolished the effect of ectopically expressed Zcf37 on opaque-to-white switching, whereas ectopic expression of EFG1 promoted white cell formation without presence of Zcf37. Our results suggest that Zcf37 acts as an activator of white cell formation and a repressor of opaque state and functions upstream of Efg1.
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