The cAMP phosphodiesterase encoded by CaPDE2 is required for hyphal development in Candida albicans

Abstract

The cAMP-dependent pathway, which regulates yeast-to-hypha morphogenesis inCandida albicans, is controlled by changes in cAMP levels determined by the processes of synthesis and hydrolysis. Both low- and high-affinity cAMP phosphodiesterases are encoded in theC. albicansgenome.CaPDE2, encoding the high-affinity cAMP phosphodiesterase, has been cloned and shown to be toxic inSaccharomyces cerevisiaeupon overexpression under pGAL1, but functional under the moderate pMET3. Deletion ofCaPDE2causes elevated cAMP levels and responsiveness to exogenous cAMP, higher sensitivity to heat shock, severe growth defects at 42 °C and highly reduced levels ofEFG1transcription.In vitroin hypha-inducing liquid mediumCaPDE2, deletion prohibits normal hyphal, but not pseudohyphal growth. On solid mediumcapde2mutants form aberrant hyphae, with fewer branches and almost no lateral buds, which are deficient in hypha-to-yeast reversion. The phenotypic defects ofcapde2mutants show that the cAMP-dependent pathway plays specific roles in hyphal and pseudohyphal development, its regulatory role however, being greater in liquid than on solid mediumin vitro. The increased expression ofCaPDE2after serum addition correlates well with a drop in cAMP levels following the initial rise in response to the hyphal inducer. These results suggest that Capde2p mediates a desensitization mechanism by lowering basal cAMP levels in response to environmental stimuli inC.albicans.