REASSESSMENT OF THE EFFECT OF GLUCAGON AND NUCLEOTIDES ON CANDIDA-ALBICANS GERM TUBE FORMATION

The role of cyclic AMP in the process of germ tube formation in Candid a albicans was investigated. The exogenous supply of the nucleotide or of agents that raise its intracellular levels stimulated germination induced by N-acetyl-D-glucosamine; glucagon showed this same stimulato ry effect on yeast cell transition to the hyphal form. Compounds, incl uded glucagon, that stimulated hyphal formation, also notably enhanced the development of hyphae. The stimulatory effect of glucagon on germ ination was blocked by the specific antagonist des His(1) [Glu(9)] glu cagon amide, probably indicating an interaction of the hormone with a glucagon-like receptor on the membrane of the cells. Indirect immunofl uorescence experiments showed that glucagon binds to the yeast cell su rface. When N-acetyl-D-glucosamine was replaced by serum as inducing a gent of germination, the stimulatory effect of glucagon was substantia lly augmented, the resulting of germination being more than 2.5-fold g reater than that attained in the presence of N-acetyl-D-glucosamine; m oreover, the glucagon concentration needed for half maximal stimulator y activity with serum as inducing agent was at least 50-fold lower tha n with N-acetyl-D-glucosamine. Monoclonal and polyclonal anti-glucagon antibodies blocked the effect of the hormone. An interesting result o bserved during these experiments was the fact that a definite period o f incubation of C. albicans yeast cells with N-acetyl-D-glucosamine as inducer commits them to hyphal development. When serum was used as in ducer, only yeast cells evaginated during the initial incubation perio d evolved to the hyphal form upon further incubation in the absence of serum.