Hyphal induction under the condition without inoculation in Candida albicans is triggered by Brg1-mediated removal of NRG1 inhibition.

Candida albicans can switch between yeast and hyphae growth forms, which is critical for its pathogenesis. Diluting from saturated cells into fresh medium at 37°C is routinely used to induce hyphae, which depends on the cAMP-PKA pathway-activated transcriptional down-regulation of NRG1 and degradation of Nrg1 protein triggered by inoculation. It is reported that N-acetylglucosamine (GlcNAc), serum or neutral pH could stimulate filamentation in log phase cells, whereas how C. albicans develops hyphae without inoculation remains unknown. Here, we show that NRG1 down-regulation is necessary for hyphal growth under this condition. Instead of cAMP-PKA pathway, GlcNAc sensor Ngs1 is responsible for the down-regulation of NRG1 upon GlcNAc induction in log phase cells through its N-acetyltransferase activity. From a genetic screen, Brg1 is found to be essential for hyphal development without inoculation. Ngs1 binds to BRG1 promoter to induce its expression in GlcNAc. Importantly, constitutively expressed BRG1 induces NRG1 down-regulation even in the absence of GlcNAc or Ngs1. Serum or neutral pH-induced filamentation in log phase cells is also through Brg1-mediated NRG1 down-regulation. Our study provides a molecular mechanism for how C. albicans forms hyphae in different cell states. This flexibility may facilitate C. albicans to adapt varied host environment during infection.