N-ACETYL-D-GLUCOSAMINE INDUCES GERMINATION IN CANDIDA-ALBICANS THROUGH A MECHANISM SENSITIVE TO INHIBITORS OF CAMP-DEPENDENT PROTEIN-KINASE

The present study examines the involvement of cAMP-dependent protein k inase (PKA) in the dimorphic transition of Candida albicans by assessi ng the in vivo effect of two permeable PKA inhibitors on N-acetyl-D-gl ucosamine (GlcNAc)- and serum-induced differentiation. The permeable m yristoylated derivative of the heat-stable PKA inhibitor (MyrPKI), whi ch inhibited C. albicans PKA in vitro, caused a concentration-dependen t inhibition of germ-tube formation in cultures induced to germinate b y GlcNAc; germination halted irrespective of the time of addition of t he inhibitor. MyrPKI also blocked dibutyryl-cAMP (dbcAMP)- and glucago n-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 ac tivation of PKA plays a pivotal role in the biochemical mechanism unde rlying morphogenesis. CELL SIGNAL 10;10:713-719, 1998. (C) 1998 Elsevi er Science Inc.