Farnesol-mediated inhibition of Candida albicans yeast growth and rescue by a diacylglycerol analogue

Abstract

During Candida albicans yeast cell growth to early stationary phase, metabolites accumulate in the medium, including the quorum-sensing molecule farnesol. We found that besides germ tube inhibition, 40 microM farnesol also inhibited C. albicans yeast growth under yeast growth permissive conditions. Consistent with this observation, transcriptional analysis of yeast cells resuspended in fresh medium with 40 microM farnesol revealed that genes involved in hyphal formation, GTPase activation, mitosis and DNA replication were downregulated many-fold. Farnesol-mediated inhibition of yeast growth was dependent on the growth phase of the C. albicans cells. The growth defect was relieved by addition of a diacylglycerol analogue, implicating phosphatidylinositol signalling in the delay. Although diacylglycerol is an activator of protein kinase C (PKC) in mammalian cells, there is some question about activation of fungal PKCs. A mutant strain deleted for PKC1 responded to farnesol and the diacylglycerol analogue similar to wild-type, suggesting that PKC is not the target of the diacylglycerol analogue.