Inhibition of yeast-to-hypha transition in Candida albicans by phorbasin H isolated from Phorbas sp

Phorbasin H is a diterpene acid of a bisabolane-related skeletal class isolated from the marine sponge Phorbas sp. In this study, we examined whether phorbasin H acted as a yeast-to-hypha transition inhibitor of Candida albicans . Growth experiments suggest that this compound does not inhibit yeast cell growth but inhibits filamentous growth in C . albicans . Northern blot analysis of signaling pathway components indicated that phorbasin H inhibited the expression of mRNAs related to cAMP–Efg1 pathway. The exogenous addition of db-cAMP to C . albicans cells had no influence on the frequency of hyphal formation. The expression of hypha-specific HWP1 and ALS3 mRNAs, both of which are positively regulated by the important regulator of cell wall dynamics Efg1, was significantly inhibited by the addition of phorbasin H. This compound also reduced the ability of C . albicans cells to adhere in a dose-dependent manner. Our findings suggest that phorbasin H impacts the activity of the cAMP–Efg1 pathway, thus leading to an alteration of C . albicans morphology.