Effect of nucleosides and nucleotides and the relationship between cellular adenosine 3′:5′-cyclic monophosphate (cyclic AMP) and germ tube formation in Candida albicans

A yeast-mycelium (Y-M) transition in Candida albicans was induced by exogenous yeast extract, adenosine, adenosine 5′-monophosphate (AMP), adenosine 5′-diphosphate (ADP), adenosine 3′:5′ cyclic monophosphate (cAMP) and its analogue N⁶, O^2′-dibutyryl adenosine 3′:5′-cyclic monophosphate (dbcAMP) in defined liquid medium at 25°C. Adenosine 5′-triphosphate (ATP) was found to delay germ tube formation in yeast cells, whereas the cAMP phosphodiesterase inhibitors, theophylline and caffeine, induced a Y-M transition. Intracellular and extracellular cyclic AMP levels increased during the yeast-mycelium transition and maximum levels of intracellular cyclic AMP coincided with maximum germ tube formation. Of the many inducers and inhibitors of germ tube and mycelium formation in C. albicans tested, including incubation at 37°C or in the presence of 1.5mM CaCl₂, the calmodulin inhibitor calmidazolium (R24571) added together with CaCl₂ induced the highest intra- and extracellular cyclic AMP levels. These results confirm the involvement of cyclic AMP in the yeast-mycelium transition of C. albicans.