Hyphae-yeast transition induced by gladiolin

ABSTRACT: In natural and host environments, microbes experience nutritional stress and deal with inhibitory metabolites produced by competitors within microbial populations. To adapt to such conditions, the human commensal and pathogen Candida albicans uses a cell type transition between invasive hyphae and budding yeast cells. Successful commensal colonisation and virulence of C. albicans depend upon the reversibility of this transition. Yet, while one direction - from yeast to hyphae, is well understood, the other - from hyphae back to yeast, is poorly defined. To understand it, we developed an imaging assay to visualise and quantify the hyphae-to-yeast transition in real time. Using this approach, we discovered that gladiolin, a polyketide produced by Burkholderia gladioli, accelerates the C. albicans hyphae-to-yeast transition. Mechanistically, gladiolin reprograms fungal metabolism, whereby glycolysis and ergosterol biosynthesis are up-regulated. Consequently, in the presence of gladiolin C. albicans depletes glucose more rapidly and increases ergosterol content in membranes. Building on these findings, we show that glycolysis is critical for maintaining the hyphal state. Furthermore, glucose depletion constitutes the metabolic signal for the hyphae-to-yeast transition by acting on the Ras-PKA pathway. We characterised the transcriptional programs that regulate the hyphae-to-yeast transition by balancing carbon and lipid metabolism, and propose that glycolysis provides acetyl-CoA for the biosynthesis of ergosterol to sustain membrane biogenesis during hyphal elongation. We conclude that, within fungal growth niches, changing nutritional environments and dynamic regulation of fungal metabolism control the reversible transition between hyphae and yeast and determine cell type.

ORGANISM(S): Candida albicans

PROVIDER: GSE297975 | GEO | 2026/07/03

REPOSITORIES: GEO