title: N-acetyl-D-glucosamine induces germination in Candida albicans through a mechanism sensitive to inhibitors of cAMP-dependent protein kinase.
abstract: The present study examines the involvement of cAMP-dependent protein kinase (PKA) in the dimorphic transition of Candida albicans by assessing the in vivo effect of two permeable PKA inhibitors on N-acetyl-D-glucosamine (GlcNAc)- and serum-induced differentiation. The permeable myristoylated derivative of the heat-stable PKA inhibitor (MyrPKI), which inhibited C. albicans PKA in vitro, caused a concentration-dependent inhibition of germ-tube formation in cultures induced to germinate by GlcNAc; germination halted irrespective of the time of addition of the inhibitor. MyrPKI also blocked dibutyryl-cAMP (dbcAMP)- and glucagon-stimulated germination but did not affect serum-induced germination. H-89, another highly specific PKA inhibitor, displayed the same effect on germination. Neither MyrPKI nor H-89 had any effect on budding of yeast cells. In conclusion, our results indicate that cAMP-mediated activation of PKA plays a pivotal role in the biochemical mechanism underlying morphogenesis.
authors.affiliation: Programa de Investigaciones Bioquímicas y Fisiológicas (CIBYF-CONICET), Cátedra de Microbiología, Facultad de Agronomía, Universidad de Buenos Aires, Argentina.
authors.forename: R
authors.initials: R
authors.lastname: Castilla
authors.forename: S
authors.initials: S
authors.lastname: Passeron
authors.forename: M L
authors.initials: ML
authors.lastname: Cantore
mesh_terms: D000117:Acetylglucosamine / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D009024:Morphogenesis; D013449:Sulfonamides
chemical_list: D004791:Enzyme Inhibitors; D007546:Isoquinolines; D013449:Sulfonamides; D003994:Bucladesine; D005934:Glucagon; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D000117:Acetylglucosamine