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.

Virulence Factors as Promoters of Chronic Vulvovaginal Candidosis: A Review

“…Notably, several host genetic mutations have already been associated with a potential risk factor for relapsing, such as mutations in the NLRP3 gene, which enable activation of caspase-1 and mutations in the TLR2 gene, which are related to increase or decrease in host organism response/defense [32]. Another possible factor of VVC chronicity was associated with high Candida spp resistance rates to treatment [33,34].…”

Erg6 Acts as a Downstream Effector of the Transcription Factor Flo8 To Regulate Biofilm Formation in Candida albicans

“…The transcription factor Flo8 acts downstream of the cAMP-protein kinase A (PKA) pathway and interacts with Efg1 to regulate hyphal growth ( 12 ). Flo8 is also required for biofilm development within 48 h ( 13 ). flo8 -deficient strains fail to form filaments and biofilms and are avirulent in systemically infected mouse models ( 12 ).…”

5 / Protein kinase A governs growth and virulence in Candida tropicalis

“…Interestingly, the tpk1/tpk1 tpk2/tpk2 mutant showed upregulation of four transcription factors (BCR1, FLO8, GAL4, and RIM101) in C. tropicalis (Fig. 8), all of which have demonstrated roles in adherence or biofilm formation in C. albicans [45][46][47][48].…”