Inhibitors of protein phosphorylation including the retinoblastoma proteininduce germination of Candida albicans

It has been previously shown that the induction of germination in Candida a lbicans occurs following its cessation of growth as a yeast. Similarly, mam malian cells undergo a differentiation process that is preceded by a growth cessation associated with a hypophosphorylation of proteins of the retinob lastoma gene family. It is postulated that a similar type of mechanism may be operative in C, albicans and protein phosphorylation inhibitors: forskol in (stimulates cyclic adenosine monophosphate production), okadaic acid (ph osphatase inhibitor) and D-erythro-sphingosine (retinoblastoma protein phos phorylation inhibitor) have been used to further strengthen this hypothesis . Okadaic acid (1-1000 nM) and D-erythro-sphingosine (100 mu M) significant ly inhibited the growth of yeast cells of C. albicans. D-Erythrosphingosine at 1000 mu M was candidicidal. Forskolin did not significantly affect grow th. Exponentially grown C. albicans pretreated with forskolin (10 mu M), ok adaic acid (1000 nM) or D-erythro-sphingosine (100 mu M) readily germinated . In comparison, when these inhibitors were incorporated in the same medium , germination of exponentially grown cells did not occur. These results sug gest that protein dephosphorylation may be necessary at an early stage of t he yeast-hyphae transition in C. albicans.