ABSTRACT
The fungal pathogen Candida albicans can transition from budding to hyphal growth, which promotes biofilm formation and invasive growth into tissues. Stimulation of adenylyl cyclase to form cAMP induces hyphal morphogenesis. The failure of cells lacking adenylyl cyclase (cyr1Δ) to form hyphae has suggested that cAMP signaling is essential for hyphal growth. However, cyr1Δ mutants also grow slowly and have defects in morphogenesis, making it unclear whether hyphal inducers must stimulate cAMP, or if normal basal levels of cAMP are required to maintain cellular health needed for hyphal growth. Interestingly, supplementation of cyr1Δ cells with low levels of cAMP enabled them to form hyphae in response to the inducer N-acetylglucosamine (GlcNAc), suggesting that a basal level of cAMP is sufficient for stimulation. Furthermore, we isolated faster-growing cyr1Δ pseudorevertant strains that can be induced to form hyphae even though they lack cAMP. The pseudorevertant strains were not induced by CO2 , consistent with reports that CO2 directly stimulates adenylyl cyclase. Mutational analysis showed that induction of hyphae in a pseudorevertant strain was independent of RAS1, but was dependent on the EFG1 transcription factor that acts downstream of protein kinase A. Thus, cAMP-independent signals contribute to the induction of hyphal responses.
Subject(s)
Candida albicans/growth & development , Candida albicans/metabolism , Cyclic AMP/metabolism , Hyphae/growth & development , Signal Transduction , Acetylglucosamine/pharmacology , Adenylyl Cyclases/deficiency , Adenylyl Cyclases/genetics , Candida albicans/drug effects , Candida albicans/genetics , Cyclic AMP/pharmacology , Cyclic AMP-Dependent Protein Kinases/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Fungal Proteins/genetics , Gene Expression Regulation, Fungal , Hyphae/drug effects , Hyphae/genetics , Hyphae/physiology , Signal Transduction/genetics , Transcription Factors/geneticsABSTRACT
N-acetylglucosamine (GlcNAc) has long been known to play important roles in cell surface structure. Recent studies are now revealing new functions for GlcNAc in cell signaling. Exposure to GlcNAc regulates virulence functions in the human fungal pathogen Candida albicans and in pathogenic bacteria. These signaling pathways sense exogenous GlcNAc and are distinct from the O-GlcNAc signaling pathways in mammalian cells in which increased levels of intracellular GlcNAc synthesis leads to post-translational modification of proteins by attachment of O-GlcNAc. The novel roles of GlcNAc in cell signaling will be the subject of this mini-review.
