Hyphal development in Candida albicans from different cell states.

Candida albicans is an important opportunistic fungal pathogen of immunocompromised individuals. The ability to switch between yeast, pseudohyphal, and hyphal growth forms (polymorphism) is one of the most investigated virulence attributes of C. albicans. The usual method for inducing hypha formation in the lab is by diluting cells from a saturated culture into fresh medium at 37 °C. The molecular mechanism at action under these conditions has been previously investigated. C. albicans can also form hyphae in growing cells without dilution. The ability of C. albicans to form hyphae in different cell states facilitates the fungus to adapt varied host environments during infection. A recent study by Su et al. uncovered the molecular mechanism for how C. albicans develops hyphae under the condition without inoculation. N-Acetylglucosamine (GlcNAc) stimulates filamentation in log phase cells through transcriptional down-regulation of NRG1, the major repressor of hyphal development. Instead of cAMP-PKA pathway, GlcNAc sensor Ngs1 is responsible for this process. Ngs1 binds to GlcNAc to activate its N-acetyltransferase activity, leading to the induction of BRG1 expression. The increased level of BRG1 could repress NRG1 transcripts, resulting in hyphal growth. Hyphal development in log phase cells induced by serum or neutral pH also requires activation of BRG1 to down-regulate NRG1 transcription. Therefore, hyphal induction under the condition without inoculation is trigged by Brg1-mediated removal of Nrg1 inhibition. This review describes our current understanding of the molecular mechanism underlying hyphal development, the best studied virulence factor in C. albicans. These will expand the number of potential drug targets with novel modes of action for anti-virulence therapeutics.