title: cAMP-independent signal pathways stimulate hyphal morphogenesis in Candida albicans.
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 CO2directly 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.
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY, USA.|Graduate Program in Molecular and Cellular Biology, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Salvatore M
authors.initials: SM
authors.lastname: Parrino
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Si
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Shamoon
authors.initials: S
authors.lastname: Naseem
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Groudan
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY, USA.|Graduate Program in Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Gardin
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY, USA.
authors.forename: James B
authors.identifier: 0000-0001-5989-4086
authors.initials: JB
authors.lastname: Konopka
mesh_terms: D000117:Acetylglucosamine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000172:deficiency / Q000235:genetics; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D025301:Hyphae / Q000187:drug effects / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D005656:Fungal Proteins; D014157:Transcription Factors; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D000117:Acetylglucosamine