Hyphal induction under the condition without inoculation in <italic>Candida albicans</italic> is triggered by Brg1‐mediated removal of <italic>NRG1</italic> inhibition.

Summary: <italic>Candida albicans</italic> 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 <italic>NRG1</italic> 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 <italic>C. albicans</italic> develops hyphae without inoculation remains unknown. Here, we show that <italic>NRG1</italic> 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 <italic>NRG1</italic> upon GlcNAc induction in log phase cells through its <italic>N</italic>‐acetyltransferase activity. From a genetic screen, Brg1 is found to be essential for hyphal development without inoculation. Ngs1 binds to <italic>BRG1</italic> promoter to induce its expression in GlcNAc. Importantly, constitutively expressed <italic>BRG1</italic> induces <italic>NRG1</italic> 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 <italic>NRG1</italic> down‐regulation. Our study provides a molecular mechanism for how <italic>C. albicans</italic> forms hyphae in different cell states. This flexibility may facilitate <italic>C. albicans</italic> to adapt varied host environment during infection. [ABSTRACT FROM AUTHOR]