Mutations in the Flo8 transcription factor contribute to virulence and phenotypic traits in Candida albicans strains

Abstract

The ability of Candida albicans to switch between multiple morphological states, including yeast (blastospores), fliamentous, pseudohyphal and hyphal forms, has been shown to be important for its pathogenicity and virulence. The transcription factor Flo8, which contains the LisH domain, is a downstream regulator of the cAMP/PKA pathway. Four clinical strains from adult women with recurrent vaginitis were isolated, and their morphology was observed. The results showed that two strains presented longer hyphal threads, stronger adherence to plastic and invasion into agar medium, and one strain was defective in filament and biofilm growth. Interestingly, mutations in the FLO8 gene were identified in these strains. We analyzed the contribution of these mutants to filamentous growth by constructing mutant strains and investigating their morphological and ultrastructural characteristics, including putative virulence traits, in vitro and in vivo. The results showed that the G723R and T751D Flo8 mutants enhanced activation of the Flo8C terminus, thereby promoting filamentous growth and increasing virulence.