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

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 mu M 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 mu M 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 PKCI responded to farnesol and the diacylglycerol analogue similar to wild-type, suggesting that PKC is not the target of the diacylglycerol analogue. Copyright (c) 2007 John Wiley & Sons, Ltd.