Mrv6 modulates membrane ergosterol homeostasis to control hyphal signaling and virulence in Candida albicans

While this rigid membrane structure shielded the fungus from exogenous toxins, it fatally restricted the intracellular entry of morphogenetic signals under hypoxic conditions. As a result of this sensing blockade, the major filamentous repressor NRG1 remained aberrantly highly expressed, trapping the pathogen in an avirulent yeast state. Crucially, targeted genetic suppression of either ERG1 or NRG1 effectively bypassed this signaling blockade, restoring morphogenetic switching and pathogenicity in the mrv6Δ mutant.

Collectively, our findings reveal an unprecedented pathogenic strategy where C. albicans rewires ergosterol homeostasis via a stress-responsive protein to modulate membrane permeability, highlighting Mrv6 as a novel mechanosensory node connecting the DNA damage response to environmental sensing and full virulence.